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RC1 06  .Ot8  Fever,  its  thermotax 


RECAP 


VER 


T  S    T  H  E  R  M  O  TAX  I S 
AND  METABOLISM 


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SAAC     OTT 


ii^\o(o  Ota 


^AtUrmtt  SItbrarg 


FEVER,  ITS  THERMOTAXIS 
AND  METABOLISM 


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FEVER 

ITS  THERMOTAXIS  AND 
METABOLISM 


BY 

ISAAC  OTT,  A.M.,  M.D. 

Professor   of   Physiology   Medico-Chirurgical    College,    Philadelphia,    Member    of 
American  Physiological  Society,  Ex-president  of  American  Neurological  Asso- 
ciation, Consulting  Neurologist  Norristown  Asylum,  Member  of  the  Deut- 
sche Medicinischen  Gesellschaft  of  New  York,  Member  of  Vereinigung 
Alter  Deutschen  Studenten  in  Amerika,  American  Society  for  Phar- 
macology and  Experimental  Therapeutics,  Society  for  Experi- 
mental Biology  and  Medicine,   Member  of  The  American 
Association  for  the    Advancement   of    Science,   Corre- 
sponding Member  of  Atlanta  Academy  of  Medicine, 
Member   of    Philadelphia   Medical    Club    and 
Chemists'  Club  of  New  York,  etc. 


PAUL  B.   HOEBER 

67-69  E.  59TH  STREET 

NEW    YORK 

1914 


Copyright,  1914 
By  PAUL  B.  HOEBER 


Published  December,  1914 


Printed  in  U.  S.  A. 


Dedicated  to  the 
Memory  of  my  Father, 

JACOB  OTT 


' '  Animalia  in  accessibus  f ebrium  intermit- 
tentium  a  priucipio  frigore  et  horrore  cor- 
ripiunter  sed  paulo  post  majorem  in  modnm 
incalescunt.  quod  etiam  faciunt  a  principio 
in  causonibus  et  f ebribus  pestilentialibus. ' ' 

' '  Qualis  vero  gradus  sit  caloris  in  cerebro, 
stomacho,  corde  et  reliquis,  similiter  ad  hue 
non  est  quaesitium. "  Bacon,  Novum  Or- 
ganum.     Lib.  II,  13. 


PEEFACE 

These  three  lectures  were  delivered  be- 
fore the  Sophomore  Class  of  the  Medico- 
Chirurgical  College.  They  have  been 
thought  worthy  of  publication,  as  the  sub- 
ject is  one  of  maximal  importance  in  the 
practice  of  medicine.  The  studies  upon 
this  subject  have  occupied  the  author  for 
forty-five  years,  as  a  practitioner  of  medi- 
cine and  a  physiologist. 

Isaac  Ott. 


ILLUSTRATIONS 

Fig.     1     Showing  tuber   cinereum   in  man  page 

Facing  page     24 

Fig.     2     Thermo-inliibitoiy  centers  in  cat's  brain   .      37 

Fig.     3     Showing  rises  of  temperature  after  injury 

to    brain    of    man 39 

Fig.  4  Showing  effect  of  external  heat  upon 
respiration  when  corpora  striata  and 
tuber  cinereum  are  removed   ....      58 

Fig.  5  Showing  the  effect  of  a  weak  faradic  cur- 
rent to  the  tuber  upon  the  rate  of 
respiration Facing  page     60 

Fig.  6  Showing  the  effect  of  a  single  electric 
shock  to  the  tuber  causing  respiratory 
arrest Facing  page    60 

Fig.     7     Showing   effect   of   external   heat   upon    a 

normal  rabbit  as  regards  the  respiration     61 

Fig.  8  Showing  effect  of  puncture  of  tuber  cine- 
reum upon  blood  pressure 63 

Fig.     9     Composite  curve  showing  the  average  of  20 

experiments  upon  starved  animals    .      .      91 

Fig.  10     Composite  curve  showing  the  average  of  12 

experiments  upon  fevered  animals     .      .      91 

Fig.  11     Ott's  calorimeter  for  man 99 


ILLUSTRATIONS 

PAGE 
Fig.  12     Heat   production   and   heat   dissipation   in 

malarial   fever    ....   Facing  page  118 

Fig.  13     Normal  day  (Lehacheff  and  Avroroff  from 

Einger) 123 

Fig.   14     Day  of  high  fever   (Lehacheff  and  Avroroff 

from  Ringer) 129 


LECTUKE  I 


FEVER,  ITS  THERMOTAXIS 
AND  METABOLISM 

LECTURE  I 

Gtentlemen: — In  the  opening  course  of 
physiology  for  this  year  I  shall  invite  yonr 
attention  to  a  subject  which  will  engage 
your  minds  every  day  that  you  practice 
medicine.  I  refer  to  fever.  In  my  prac- 
tice of  many  years  it  has  been  a  daily, 
omnipresent  factor.  It  is  the  alarm  of  the 
family,  sometimes  a  sign  of  impending 
death  and  often  a  puzzle  to  the  physician. 
The  process  of  fever  has  been  a  difficult 
problem  for  the  last  two  thousand  years. 
The  fever  may  be  a  gentle  wave,  or  every 
cell  may  surge,  boil  and  burn,  while  the  vi- 
brations run  to  and  fro  until  they  overflow 
and  the  scissors  of  Atropos  and  the  Styg- 
ian boat  of  Charon  end  all. 

13 


14  ISAAC  OTT:  FEVER 

The  questions  now  arise,  What  has 
thrown  a  strong  man  into  fever?  Why 
has  the  temperature  suddenly  run  up? 
Where  is  the  central  point  of  this  heat 
which  is  like  a  fire  in  his  veins  ? 

The  study  of  fever  includes  bacteriology, 
immunity  and  pathological  physiology. 
Aristotle  thought  heat  was  developed  in 
the  right  heart;  Galen  placed  its  origin  in 
the  left  heart,  the  so-called  flammula 
cordis,  and  this  was  taught  up  to  1660. 
Bacon,  in  the  '^  Novum  Organum,"  defined 
heat  as  an  expansive  motion  amongst  the 
minute  particles  of  bodies,  which  is  the 
conclusion  at  which  the  most  eminent  phys- 
icists have  arrived.  Tyndall  ^  quotes  a 
considerable  portion  of  Bacon's  twentieth 
aphorism  as  illustrating  the  theory  which 
he  has  himself  so  ably  and  clearly  ex- 
pounded. 

In  the  seventeenth  century.  Van  Hel- 
mont  spoke  of  heat  as  produced  in  the 

1  Tyndall.     "Heat  and  Mode  of  Motion,"     Appendix. 


TIIERMOTAXIS  AND  METABOLISM     15 

lieart  by  a  mixture  of  sulpliur  and  the  vola- 
tile salts  of  the  blood. 

Lavoisier,  in  1775,  first  showed  that  the 
heat  of  animals  was  due  to  the  combus- 
tion of  oxygen.  He  also  proved  that  the 
quantity  of  oxygen  absorbed  and  of  C02 
excreted  depended  upon  food,  work  and 
temperature.  In  1783,  Lavoisier  and  La 
Place  ^  made  calorimetrical  and  respira- 
tory studies  upon  a  guinea  pig.  Lavoisier 
also  knew  that  nitrogen  gas  had  nothing 
to  do  with  respiration.  These  calorimet- 
rical studies  were  followed  by  experiments 
with  a  water  calorimeter  by  Crawford  ^ 
and  by  Dulong  and  Von  Despretz,*  whose 
calorimeter  is  still  a  model  for  all  subse- 
quent water  calorimeters  up  to  the  present 
day. 

2  "Lavoisier  et  de  La  Place  Memoire  sur  Chaleur." 
1780. 

3  Crawford,  "Experiments  and  Observations  on  Ani- 
mal Heat."     London.     1788. 

4  Despretz.  "Recherch6s  experimentales  sur  les  causes 
de  chaleur  animale."  "Annales  de  Chimie  et  de  Phy- 
sique."    Tome  26;   1824.     P.  337. 


16  ISAAC  OTT:  FEVER 

Then  Eegnault  and  Reiset,^  in  1850,  with 
their  respiration  apparatus  studied  the 
gaseous  exchanges  of  animals,  called  indi- 
rect calorimetry.  G.  A.  Hirn,^  in  1857, 
studied  calorimetry  of  man. 

Brodie  '  held  that  the  nervous  system 
was  the  center  of  heat,  whilst  respiration 
cooled  the  animal. 

LeFevre  ^  has  shown  that  the  relation 
between  the  amount  of  heat  and  the  amount 
of  oxygen  is  not  constant.  D'Arsonval 
has  shown  that  the  curves  of  production 
of  heat  and  the  absorption  of  0  are  not 
concordant;  in  sleep,  for  example,  the  pro- 
duction of  heat  falls  to  a  minimum,  whilst 
the  consumption  of  oxygen  is  not  lowered 
to  a  corresponding  degree. 

Laulanie  ^  found  no  fixed  proportion  be- 

5  Regnault  et  Reiset.     "Annales  de  Chimie  et  de  Phy- 
sique."    1849. 

6  Hirn,     "Recherches  sur  Tequivalent  mecanique  de  la 
chaleur."     Colmar.     1858. 

7  Brodie.     "Philosophical  Transactions."     1811. 

8  LeFevre.     "Chaleur  animale."     1911.     P.  76. 
»  Laulanie. 


THERi\IOTAXIS  AND  METABOLISM      17 

tween  heat  production  and  the  respiratory 
gases  exchanged. 

Then  Pettenkofer  and  Voit  ^^  built  their 
splendid  respiration  apparatus  and  created 
in  Munich  the  first  school  for  metabolism, 
which  has  produced  many  workers  now 
prominent  in  the  scientific  world. 

But  in  the  respiration  calorimeter  of  At- 
water  ^^  and  Benedict  we  have  direct  cal- 
orimetry  and  indirect  calorimetry  (or  the 
gaseous  exchanges)  combined.  Their  ap- 
paratus is  nearly  perfect  for  the  study  of 
animal  heat  and  by  its  use  they  have  again 
verified  the  law  of  conservation  of  energy 
and  solved  many  other  problems  in  metab- 
olism. 

Hence,  the  three  methods  of  studying  the 
phenomena  of  heat  are:  (1)  by  the  ther- 
mometer (probably  discovered  by  Galileo 
and  used  by  Sanctorius),  (2)  by  the  cal- 

10  Pettenkofer    und    Voit.     "Zeitschrift    f.    Biologie." 
1866.     Band  11,  p.  478. 

11  Atwater.     "A  Respiration  Calorimeter,"     1884. 


18  ISAAC  OTT:  FEVER 

orimeter,  and  (3)  by  the  amount  of  oxygen 
absorbed  and  the  amount  of  C02  elim- 
inated (indirect  calorimetry ) . 

THEBMOTAXIS 

Before  we  take  up  the  subject  of  fever, 
I  will  call  your  attention  to  that  of  thermo- 
taxis,  which  means  heat  regulation,  so 
that  the  temperature  is  kept  on  an  average 
for  24  hours  at  about  98.4°  F. 

Now  thermotaxis  depends  upon  four 
nervous  centers:  two  basal  thermogenic 
centers — the  corpus  striatum  and  the  chief 
one,  the  tuber  cinereum — and  two  inhib- 
itory cerebral  centers — the  cruciate  and 
sylvian. 

In  April,  1884,  I  ^-  published  amongst 
others  the  following  experiments. 

Experiment  2.  Eabbit.  Weight  of  ani- 
mal 7%o  pounds.  (Here  there  was  a 
transverse  section  of  the  corpora  striata.) 

12  Ott.  Journal  of  'Nervous  and  Mental  Diseases. 
\'ol.  XI,  No.  2,  page  141,  April,  1884. 


THERMOTAXIS  AND  METABOLISM      19 


Time  P.  M. 

Calorimeter  Temp. 

Rectal  Temp. 

12.25 

84.86 

10P^°  F. 

1.55 

104%°  F. 

3.15 

104%°  F. 

4.30 

11B^°  F. 

Rise  of  6%°  F. 

Experiment  3.  Cat;  weiglit  5^%o 
pounds;  transverse  section  tlirough  the 
middle  of  the  corpora  striata. 


Time  P.  M. 

Calorimeter  Temp.      Rectal  Temp. 

12.25 

74.50                      102%°  F. 

1.40 

102%°  F. 

2.30 

106%°  F. 

3.45 

107%°  F. 

Rise  of  4%°  F. 

It  is  from  these  and  other  experiments 
that  I  claim  the  discovery  of  the  thermo- 
genic center  in  the  corpus  striatum. 

In  October,  188-4,  Sachs  and  Aron- 
sohn  ^^  published  a  paper,  six  months  after 

isDuBois.     Archiv.  f.  Physiologic,  Oct.  31,  1SS4. 


20  ISAAC  OTT:  FEVER 

mine,  stating  tliat  there  was  a  thermogenic 
center  in  the  corpus  striatum  and  that  it 
was  located  mainly  in  the  caudate  nucleus. 
They  also  found  an  increased  production 
of  urinar^^  nitrogen,  an  increased  absorp- 
tion of  oxygen  and  an  increased  elimina- 
tion of  carbon  dioxide.  The  increase  of 
nitrogen  in  the  urine  they  inferred  was 
due  to  a  using  up  of  the  protein.  They 
did  not  make  any  calorimetrical  studies 
to  determine  positively  if  the  increase  of 
temperature  was  due  to  increased  produc- 
tion of  heat  or  to  diminished  dissipation. 
They  offered  no  proof,  except  gaseous 
exchange  and  the  urinary  nitrogen,  of 
their  conclusion  that  the  rise  of  temper- 
ature was  due  to  increased  production  of 
heat. 

In  September,  1887,  Ott  ^^  and  W.  A. 
Carter  (at  that  time  a  medical  student) 
first  showed  calorimetrically  that  the  rise 

14  Ott    and    Carter.     Therapeutic    Gazette.     Sept.    15, 
1887. 


THERMOTAXIS  AND  METABOLISM      21 

of  temperature  after  puncture  of  tlie 
corpus  striatum  was  due  to  increased  pro- 
duction and  not  to  diminished  dissipation 
of  heat.  Thus  in  experiment  2,  in  a  rab- 
bit with  a  puncture  into  the  right  corpus 
striatum,  the  temperature  rose  2.7°  F., 
whilst  heat  production  before  the  puncture 
was  13.70  B.  H.  units  and  after  the  punc- 
ture 22.50  heat  units ;  heat  dissipation  be- 
fore puncture  was  16.68  heat  units  and 
after  puncture  18.77  heat  units.  I  first 
proved  the  existence  of  a  thermogenic  cen- 
ter in  the  corpus  striatum  and  also  first 
established  the  fact  that  the  increase  of 
temperature  was  due  to  increased  produc- 
tion of  heat  and  not  to  coincident  dimin- 
ished dissipation. 

The  claim  of  Eichet  ^^  to  have  been  the 
first  to  discover  the  thermogenic  centers 
cannot  be  upheld.  All  that  he  claimed  was 
that  puncture  of  the  anterior  part  of  the 

15  Riehet.     Bulletin  de  la  SocietS  de  Biologie.     March 
29,  1884. 


22  ISAAC  OTT:  FEVER 

brain  produced  hyperthermia  due  to  in- 
creased production  of  heat. 

There  was  no  localization  by  him  in  the 
corpus  striatum,  but  a  cortical  injury 
which  Eulenburg  and  Landois  before  him 
had  localized  in  the  cruciate  sulcus. 

Barbour,  H.  G.,^^  has  shown  that  the 
direct  application  of  cold  and  heat  to  the 
region  of  the  corpus  striatum  causes  the 
rectal  temperature  to  respond  by  a  change 
in  the  opposite  direction  from  that  pro- 
duced in  that  region  of  the  brain.  Cold 
(33°  C.)  applied  to  the  corpus  striatum 
causes  a  rise  in  the  temperature  of  the 
body,  associated  with  shivering  and  peri- 
pheral vaso-constriction.  Centrally  ap- 
plied heat  (42°  C),  on  the  other  hand, 
causes  a  fall  in  the  body  temperature. 

Barbour  and  Wing  ^^  have  also  sliown 
that  the  heat  regulating  centers   are  di- 

ic  Arc/ztV.  /.  Ea^p.  Path,  und  /'hurmnkol.  1012, 
LXXXT. 

17  Journal  of  Pharmacology  and  Experimenial  Thera- 
peutics, Vol.  V.     No.  2,  p.  147. 


THERMOTAXIS  AND  METABOLISM      23 

rectly  susceptible  to  the  local  action  of 
drugs,  both  fever-exciting  and  anti- 
pyretic substances. 

Barbour  and  Prince  ^"^  have  shown  that 
local  heating  of  the  corpus  striatum  in  rab- 
bits diminishes  the  Co^  output,  the  oxygen 
combustion  and  the  respiratory  volume. 

Local  cooling  of  the  same  region  gives 
precisely  the  opposite  results. 

Central  heating  reduces  the  tempera- 
ture of  the  body  not  only  by  favoring  heat 
dissipation  but  by  diminishing  heat  pro- 
duction. 

TUBER    CINEEEUM 

In  1885,  July  4,  I  ^^  published  a  prelimi- 
nary communication  stating  that  a  ther- 
mogenic center  was  localized  at  the  an- 
terior end  of  the  optic  thalami,  and  that 
the  increase  of  temperature  after  puncture 
was  due  to  increase  of  production  of  heat, 

17a  Barbour    and    Prince.     Journal    of    Pharmacology 
and  Eoop.  Therapeutics,  Vol.  VI,  No.  1,  page  1.     1914. 
IS  Ott.     Philadelphia  Medical  ^ews.     July,  1885. 


24  ISAAC  OTT:  FEVER 

as  shown  by  the  calorimeter.  The  tem- 
perature rise  was  especially  marked  when 
a  puncture  along  the  median  line  caused  a 
peculiar  shrill  cry,  a  point  to  which  Schiff 
first  called  attention,  in  the  production  of 
a  sound. 

In  March,  1887,  I  proved  that  this  rise 
of  temperature  was  due  to  increased  pro- 
duction of  heat,  as  shown  by  the  calori- 
meter, and  not  to  diminished  dissipa- 
tion. 

In  July,  1891, 1  ^^  showed  that  the  center 
about  the  anterior  ends  of  the  thalami  was 
more  accurately  located  in  the  tuber 
cinereum.  This  was  shown  by  the  method 
of  puncture. 

I  have  also  punctured  the  tuber  cinereum 
in  rabbits  by  means  of  a  dental  drill  with 
a  cross  bar  through  the  mouth  and  obtained 
a  temperature  of  109°.  This  section  does 
not  cut  any  thermogenic  fibers. 

19  Ott.  Journal  of  Nervous  and  Mental  Diseases. 
July,  1891. 


Tuberciiluiti  cinereuin 
(Hypophysis  entfernt)\ 


Chiasmiv 


N.  opticus  (II) 


Fossa  interpedunculai 
8.  Tarini 

Radix  lateralis 
d.  Tract,  opticus^ 

Radix  medialis         £ 
d.  Tract,  opticus" — 

Corpus  geniculatum--' 

laterale  / 

TJebargang  in  d.  Corpus  ,,''' 
ganiculatum  mediale 


Fasciculus  obliquus - 

pontis 


Flocculus 


Plexus  chorioideus 
lateralis  ventriculi  IV" 


Oliva/ 
Pyraraides 


Tractiis  opticus 


Fibrae  arcualae  extt.  "' 

Decussatio  pyranaidum'' 


^N.  oculomotorius  (III) 


N.  troclilearis  iIV) 


N.  trigeminus  (V) 

N.  aliducens  (VI) 

^N.  facialis  (VII) 

-N".  acusticus  (VIII) 

~"~"^X.  glossopharyngeus  (IX) 
^^^--X.  vagus  (X) 
"'^-N.  accesporius  (XI) 

N\.  hypoglossus  (XII) 
"""Xn.  cervicales 


Fig.  1. 
Showing  Tuber  Cinereuin  in  Man. 


THERMOTAXIS  AND  METABOLISM     25 

Then  Isenschmid  and  Sclinitzler,^^  after 
a  series  of  experiments,  arrived  at  the  con- 
clusion that  the  regulation  of  temperature 
was  mainly  in  the  tuber  cinereum  in  the 
rabbit;  that  the  fibers  which  run  from  the 
tuber  lie  in  the  caudal  part  of  the  mid- 
brain, widely  distributed  in  the  ventral  and 
median  part  of  a  transverse  section.  In 
the  anterior  part  of  the  mid-brain  they 
are  not  united  in  a  compact  bundle. 

They  also  state  that  the  corpus  striatum 
is  also  concerned  in  heat  regulation,  but 
that  it  plays  a  subordinate  part,  for  an 
animal  without  the  corpora  striata  and 
cerebral  hemispheres  can  regulate  its  tem- 
perature just  as  it  normally  does.  They 
state  that  thermo-regulation  depends 
mainly  upon  the  tuber  cinereum. 

Jacoby  and  Eoemer  -^  have  also  made 

20  Isenschmid  and  Schnitzler.  Archiv.  f.  Exp.  Path, 
und  PharmaJcolog.  Band  76.  Heft  3  and  4.  P.  202. 
1914,  May. 

21  Jacoby  and  Roemer.  Archiv.  f.  Exp.  Path,  und 
Pharmakol.     Band  70.     1912. 


26  ISAAC  OTT:  FEVER 

an  interesting  experiment  by  letting  a 
minute  globule  of  mercury  into  the  third 
ventricle,  which  gave  rise  to  a  decided 
rise  of  temperature. 

Streerath  ^^  believes  the  center  in  the 
anterior  part  of  the  thalamus  is  more 
powerful  than  the  one  in  the  corpus 
striatum. 

J.  Camus  and  Roussy  ^^  have  found  that 
a  lesion  at  the  base  of  the  brain  in  the 
tuber  cinereum  produced  polyuria.  Their 
experiments  were  made  on  dogs  after  ex- 
cision of  the  pituitary  through  the  mouth. 
They  state  that  in  the  tuber  cinereum  there 
is  a  zone  which  causes  polyuria.  This 
zone  also  has  a  regulating  mechanism, 
which  causes  retention  of  water  in  the  or- 
ganism. Lesions  in  this  region  are  able 
to  produce  polyuria  witli  parallel  polydip- 
sia without  disturbance  of  the  mechanism 

22  streerath.     Archiv.  f.  Physiologie.     1910.     P.  315. 

23  Camus    and    Pvoussy.     Comptes    liendus    Societd    de 
Biologie.     No.  10.     May  15,  1914.     P.  773. 


TTIERMOTAXIS  AND  METABOLISM      27 

which  causes  retention  of  water  in  the  sys- 
tem. In  young  animals  it  would  appear 
that  the  regulating  mechanism  for  the  re- 
tention of  water  is  less  perfect  than  in 
adults. 

Furthermore  of  all  the  disturbances 
which  relate  to  the  absorptional  elimina- 
tion of  water,  puncture  at  the  base  of  the 
brain  is  more  effective  and  durable  than 
injections  of  urea,  glucose,  sodium  chlo- 
ride, caffeine,  or  a  watery  diet. 

Bechterew  and  Sakovic  ^^  found  that 
puncture  of  the  tuber  cinereum  produced 
a  rise  of  temperature  and  that  this  was 
due  to  increased  heat  production,  as  shown 
by  Paschutin's  calorimeter. 

Sakovic  also  showed  that  the  carbon  di- 
oxide elimination  increased  with  the  in- 
crease of  temperature.  Bechterew  be- 
lieves that  the  region  of  the  tuber  cinereum 
has  an  undoubted  influence  upon  the  tis- 
sues of  the  organism. 

24  Sakovic.     "Dissertation."     1897.     St.  Petersburg. 


28  ISAAC  OTT:  FEVER 

Now  Isenschmid  and  Krehl  ^^  have  shown 
that  heat  regulation  was  destroyed  by 
making  sections  in  the  mid-brain,  that  is, 
when  the  animal  was  placed  in  a  warm 
chamber  it  could  not  prevent  a  rise  of 
bodily  temperature,  or,  in  a  cold  chamber, 
could  not  prevent  a  fall  of  temperature; 
in  other  words,  it  acted  like  a  cold-blooded 
animal,  the  temperature  rose  and  fell  with 
that  of  the  air.  They  arrived  at  the  con- 
clusion that  in  the  mid-brain  a  center  ex- 
isted which  regulated  the  temperature  of 
the  body. 

Citron  and  Leschke  ^^  found  on  mid- 
brain puncture  that  heat  regulation  failed, 
that  cold  lowered  and  heat  elevated  the 
temperature.  They  also  found  after  ' '  mid- 
brain puncture"  that  bacteria,  protozoa, 
anaphylactic  poison,  sodium  chloride,  col- 
loidal paraffin,  and  tetrahydro-beta-naph- 

25  Isenschmid  u.  Krehl.  A7'chii\  f.  Exp.  Path  n.  Phar- 
makol.     Band  20,  1912. 

26  Citron  and  Leschke.  Zeifschrift  f.  Exp.  Path.  u. 
Ther.     Band  14.     1913. 


THERMOTAXIS  AND  METABOLISM     29 

thylamine  produced  no  fever,  but  a  fall  of 
temperature.  They  believe  the  seat  of 
pyrogenesis  to  be  in  the  mid-brain. 

Cloetta  and  Waser  ^"^  placed  fine  thermo- 
electric elements  in  the  third  ventricle. 
They  also  inserted  thermometers  in  the 
rectum,  in  the  anterior  part  of  the  cere- 
brum, under  the  skin  and  in  other  places. 
They  then  injected  tetra-hydro-beta-naph- 
thylamine  into  the  circulation.  The  ther- 
mometric  apparatus  in  the  third  ventricle 
showed  a  rise  of  temperature  in  a  few 
seconds,  whilst  in  the  rectum,  cerebrum  and 
the  other  parts  of  the  body  the  tempera- 
ture began  to  rise  later.  Fever  producing 
agents  also  greatly  stimulated  the  thermo- 
genic functions  of  the  third  ventricle. 

As  Isenschmid  and  Schnitzler  have  said, 
the  chief  nerve  center  in  the  regulation  of 
heat  is  the  tuber  cinereum.  It  is  the  cen- 
ter where  puncture  causes  rapid  rise  of 

27  Cloetta  and  Waser.  Archiv.  f.  Exp.  Path.  u.  Phar. 
1913.     Band  73. 


30  ISAAC  OTT:  FEVER 

temperature,  mucli  more  rapid  than  after 
puncture  of  the  corpus  striatum.  I  have 
often  punctured  the  tuber  cinereum 
through  the  roof  of  the  mouth  in  a  rabbit, 
and  within  four  minutes  produced  a  tem- 
perature of  110°  F.  A  great  pyretogenic 
agent,  tetra-hydro-beta-naphthylamine,  can 
produce  fever  when  the  corpora  striata  and 
the  cortex  cerebri  have  been  removed,  as 
I  have  often  demonstrated.  Hence  the 
conclusion  that  the  tuber  cinereum  is  the 
ruling  center  in  the  heat  regulation  of 
fever. 

Cajal  states  that  the  nucleus  of  the  in- 
ternal capsule  has  cells  which  mingle  with 
the  cells  of  the  tuber  cinereum.  To  Cajal 
the  tuber  cinereum  is  a  motor  station 
placed  upon  the  projection  paths  of  the 
septum  lucidum  and  of  other  systems  of 
fibers  whose  origin  is  still  not  determined. 

The  tuber  cinereum  is  the  floor  and  an- 
terior wall  of  the  third  ventricle  and  be- 


TIIERMOTAXIS  AND  METABOLISM     31 

lono's,  according  to  Cajal,  to  the  pars  optica 
of  the  optic  thalamus.  Its  posterior  or  ac- 
cessory nucleus  resides  between  the  mam- 
millary  eminence  and  the  principal  nucleus 
of  the  tuber.  The  tuber  also  has  a  supe- 
rior nucleus  and  the  fibrillary  capsule  on 
the  surface  of  the  nucleus  hardly  separates 
it  from  the  rest  of  the  hypothalamus.^^ 

Edinger  believes  that  the  central  gray 
matter  of  the  mid-brain  contains  the  cen- 
tral apparatus  of  the  sympathetic.  The 
afferent  fibers  of  the  mid-brain  are  the 
spino-tectal  tracts  running  for  all  pur- 
poses in  Gower's  tract  and  ending  in  both 
anterior  copora  quadrigemina.  The  ef- 
ferent tract  of  the  mid-brain  is  the  rubro- 
spinal. Hence  the  tuber  cinereum  has  four 
functions :  thermogenic,  polypnoeic,  poly- 
uric  and  va so-tonic. 

28  Cajal.     "Histologie  du  Syst&me  Nerveiix."     Vol.  II, 
p.  48. 


32  ISAAC  OTT:  FEVER 

MINOR  THERMOGENIC  CENTERS  IN  THE 
SPINAL   CORD 

Spinal  Cord  and  C02.  I  ^^  liave  made  ex- 
periments upon  cats  and  rabbits,  using 
d'Arsonval's  calorimeter  and  Voit's  little 
respiration  apparatus.  After  section  of 
the  spinal  gray  matter  or  the  spinal  white 
matter  at  the  junction  of  the  dorsal  and 
lumbar  regions,  there  was  an  increase  of 
temperature  and  an  increase  of  carbon  di- 
oxide. 

Spinal  Cord  and  Heat  Production.  Ott 
and  Collmar  ^^  have  shown  that  section  of 
the  lateral  columns  of  the  spinal  cord  in 
the  cat  was  followed  by  a  rise  of  tempera- 
ture which  was  accompanied  by  an  increase 
of  heat  production  and  of  heat  dissipation, 
but  that  the  increment  of  heat  production 
was  greater  than  that  of  heat  dissipation. 

29  Ott.     Journal    of    Nervous    and    Mental    Diseases. 
Vol.  XTI.     No.  4.     October,  1885. 

30  Ott  ami  Collmar.     Journal  of  Nervous  and  Mental 
Diseases.     Vol.  XIV.     July,  1887. 


THERMOTAXIS  AND  METABOLISM      33 

Spinal  Cord,  Its  Partial  Destruction, 
Effect  on  Heat  Production.  Ott,^^  in  cats, 
destroyed  by  means  of  a  stiff  wire  the 
spinal  cord  from  the  upper  dorsal  region 
downward;  in  sections  and  destructions 
above  the  fifth  dorsal,  heat  production  fell 
nearly  one  to  two  B.  H.  units,  but  after- 
wards rose  to  about  one-third  to  one-half 
the  normal  output.  If  the  injury  was  be- 
low the  fifth  dorsal,  heat  production  nearly 
always  remained  but  little  below  the  nor- 
mal amount,  and  in  one  case  exceeded  the 
normal  amount.  In  this  case  there  could  be 
no  spinal  thermogenic  centers  connected 
with  the  cord  from  the  fifth  dorsal  down- 
ward. Whatever  spinal  thermogenic  cen- 
ter existed  must  have  been  in  the  upper 
part  of  the  spinal  cord,  that  is,  the  three 
pounds  of  the  animal,  for  the  anterior  part 
(anterior  to  the  fifth  dorsal  section),  fur- 

31  Ott.     Transactions      of      Pan-American      Congress. 
1893.     Physiological  section. 


34  ISAAC  OTT:  FEVER 

nished  the  lieat.  (Weight  of  animal  was 
five  pounds.) 

Now,  if  we  assume  for  the  sake  of  argn- 
ment  that  the  heat  produced  after  a  sec- 
tion and  destruction  of  the  cord  from  the 
fifth  dorsal  is  due  to  spinal  thermogenic 
centers,  with  muscles  and  viscera,  we  must 
assume  that  the  normal  three  pounds  of 
the  anterior  part  of  the  body  with  the 
spinal  cord  intact  above  the  fifth  dorsal 
vertebra  can  produce  as  much  heat  as  the 
normal  ^ve  pound  animal  with  an  intact 
nervous  system.  This  view  would  be  ab- 
surd. It  is  probable  that  all  the  heat  is 
produced  in  the  muscles  and  glands  and 
that  the  spinal  thermogenic  centers  are 
weak. 

That  no  thermogenic  centers  of  a  marked 
thermic  capacity  exist  in  the  pons,  medulla 
or  spinal  cord  is  proven  by  the  experi- 
ment*^^ of  injecting  tetra-hj^dro-beta- 
naphthylamine    per    jugular.    Now    this 

32  0tt.     Medical  Bulletin.     1898  and  1907. 


THERMOTAXIS  AND  METABOLISM     35 

agent  is  a  powerful  means  of  increasing 
the  temperature  to  a  high  degree,  but  if 
you  cut  behind  the  tuber  cinereum  in  a 
transverse  direction,  the  drug  is  powerless 
to  produce  any  rise  of  temperature. 

Dana  observed  a  child  with  an  absence 
of  the  cerebrum,  thalamus  and  cerebellum, 
in  which  the  temperature  was  normal. 
Here  the  tuber  cinereum,  vaso-motor,  res- 
piratory and  sweat  centers  took  on  the  act 
of  thermo-regTilation.  But  I  doubt  if  care- 
ful thermometric  observations  were  made 
at  different  parts  of  the  day  in  this  case, 
as  normal  infants  have  a  poor  regulation 
of  temperature.  A  premature  infant  of  6 
months  and  5  days  had  a  temperature  be- 
tween 94°  to  95°. 

Sternberg  and  Latzow  ^^  report  a  case 
of  hemicephalus  in  which  the  central 
nervous  system  existed  only  as  far  as  the 
locus  coeruleus,  and  there  was  marked  in- 
sufficiency of  heat  regulation. 

33  B^chterew.     '•Xervencentra."    Vol.   11,  p.   1198. 


36  ISAAC  OTT:  FEVER 

CORTICAL   THERMOTAXIC   CENTERS 

Thermo-inhibitory  Centers.  Eulenburg 
and  Landois  located  one  in  the  dog  at  the 
cruciate  sulcus.  Prof.  H.  C.  Wood 
(Senior)  showed  that  its  excision  was 
followed  by  increased  production  of  heat. 

I  have  also  located  a  center,  which  is 
called  the  sylvian,  at  the  posterior  part 
of  the  cortex.  The  existence  of  this  center 
has  been  confirmed  by  Dr.  W.  Hale  White, 
in  the  cat.  He  has  also  shown  in  a  man 
that  a  shot  from  a  pistol,  injuring  the  an- 
terior extremity  of  the  middle  lobe  of  the 
brain  and  also  the  third  frontal  convolu- 
tion, caused  a  rise  of  temperature,  104.4° 
F.  Eoughly,  this  would  correspond  to  the 
cruciate  of  the  dog. 

Page  also  reported  a  similar  case  of  de- 
pressed fracture  of  the  skull,  in  man, 
which  injured  the  posterior  part  of  the 
temporo-sphenoidal  lobe.  This  roughly 
corresponds  to  the  sylvian. 


Fig.  2. 

Thermo- inhibitory  centers  in  cat's  brain.     S,  sylvian 

C,  cruciate. 


37 


38 


ISAAC  OTT:  FEVER 


The  following  resume  expresses  my 
views  of  the  thermotaxic  centers. 

The  thermotaxic  centers  may  be  classi- 
fied as  follows: 


Thermogenic-tnber  cinereum  and 

corpus  striatum. 
Minor     thermogenic     centers     in 

spinal  cord. 
Thermo-inhibitory,    cruciate    and 

sylvian. 
Thermolytic,  polypnoeic  in  tuber 

cinereum. 
Vaso-motor  and  sudorific. 


Thermotaxic  -< 


THERMOTAXIC   NERVES 

A  thermotaxic  nerve  may  include  ther- 
mogenic, thermolytic  and  afferent  nerves 
connected  with  the  thermogenic  centers  in 
the  tuber  cinereum  and  corpus  striatum, 
which  are  concerned  with  heat  regulation. 

Boeke,^^  Botezat^^  and  De  Boer^*^  have 

3-iBoeke.     "Anatom.  Anzeiger."     1913.     B.  44. 

35  Botezat.     "Anatom.  Anzeiger."     1910.     B.  35. 

36  De  Boer.     "Fol.  Neurolog."     1913.     Band  7.     S.   1. 


THERMOTAXIS  AND  METABOLISM    39 


O 

-M 


a; 


O 


40  ISAAC  OTT:  FEVER 

shown  that  every  muscle  fiber  is  supplied 
with  sympathetic  nerves.  Hence  they  may 
contain  heat  regulating  fibers. 

There  are  some  reasons  to  believe  that 
they  run  in  the  vagus,  for  immediately 
after  section  of  the  vagi  heat  production 
falls.  There  are  reasons  to  believe  that 
they  also  run  in  the  sympathetic  nervous 
system,  and  possibly  in  the  splanchnics 
which  would  cause  more  adrenalin  and 
more  mobilization  of  glycogen  and  more 
glucose,  which  being  consumed  would  gen- 
erate more  heat. 

EFFECT  OF  SECTION  OF  VAGI  UPON  THE 

TEMPERATTJEE,  HEAT  PRODUCTION 

AND   HEAT  DISSIPATION 

I  ^"^  have  studied  the  effect  of  vagal  sec- 
tion and  found  that  the  temperature  gen- 
erally fell  immediately  and  that  heat  pro- 
duction and  heat  dissipation  also  usually 
were  diminished. 

37  Ott.     Medical  Bulletin.     1895. 


THERMOTAXIS  AND  METABOLISM     41 

Sinelnikow  ^^  found,  after  section  of  the 
spinal  cord  between  the  fourth  and  fifth 
lumbar  vertebrae  or  in  the  dorsal  region 
to  the  seventh  dorsal  vertebra,  puncture 
into  the  corpus  striatum  caused  a  rise  of 
temperature.  But  when  he  cut  out  the  ac- 
tion of  large  bundles  of  muscles  by  resec- 
tion of  the  motor  nerves  the  puncture  pro- 
duced less  rise  of  temperature.  Often  the 
temperature  rose  more  in  animals  with  ex- 
tensive paralysis  than  in  animals  able  to 
move  well.  Hence,  he  infers  that  the  punc- 
ture produces  hyper-thermia  but  not 
through  the  muscular  nerves.  When  he 
cut  the  spinal  cord  between  the  second  and 
third  dorsal  vertebrae,  the  puncture  was 
without  effect.  Here  the  visceral  glands 
are  in  great  part  removed  from  the  action 
of  the  thermogenic  center  in  the  corpus 
striatum.  If  then  it  is  the  visceral  glands 
which  are  the  chief  source  of  heat,  it  be- 
comes probable  that  several  of  the  ther- 

38  ArcHv.  /.  Physiologie.     1910.     P.  278. 


42  ISAAC  OTT:  FEVER 

motaxic  nerves  run  in  the  sympathetic 
nerves. 

Hirsch  and  Roily  came  to  the  conclusion 
that  of  the  visceral  glands,  the  liver  was 
most  important  in  the  production  of  heat. 
Now  the  cells  of  the  liver  are  supplied  by 
the  splanchnics,  and  probably  they  contain 
thermogenic  fibers. 

Schultze  ^^  cut  the  vagus  and  splanchnics 
on  both  sides  and  arrived  at  the  conclusion 
that  destruction  of  the  nervous  connections 
between  the  brain  and  the  large  abdominal 
glands  does  not  prevent  the  appearance  of 
hyperthermia  after  a  puncture  in  the 
corpus  striatum.  He  infers  that  the  hyper- 
thermia is  at  least  not  exclusively  pro- 
duced by  the  liver  and  pancreas. 

These  experiments  show  that  the  vagi 
and  splanchnics  are  not  the  only  paths  for 
thermotaxic  fibers,  that  others  also  descend 
in  the  pons,  medulla  and  the  lateral  col- 

39  ArcTiiv.  /.  Exp.  Pathol,  u.  Pharmak.  Band  43,  p. 
190. 


TIIERMOTAXIS  AND  METABOLISM     43 

umns  of  the  spinal  cord  to  the  muscles  and 
remaining  viscera. 

Ito  ^^  states  that  the  warmest  place  in 
the  body  of  the  rabbit,  after  puncture,  is 
in  the  duodenum,  even  when  the  animal  has 
been  without  food  for  several  days. 

G.  Hirsch  and  Eolly  ^^  found,  after 
curarization,  a  marked  hyperthermia  in 
rabbits  after  puncture  of  the  brain. 

Streerath  ^^  found  that  small  doses  of 
strychnia  caused  the  puncture  to  produce 
a  higher  temperature. 

All  these  thermotaxic  and  thermolytic 
centers  stand  in  a  reflex  relation  to  the  skin 
and  visceral  nerves,  probably  those  of  the 
hot  and  cold  spots,  in  the  skin  and  similar 
nerves  in  the  viscera. 

Freund   and  E.   Grafe  ^^  made   experi- 

40  Ito.     Zeitschrift  f.  Biologie.     1889.     Band  37. 
*i  Hirsch  u.   Roily.     Deiitsches  Archiv.  f.  Klin.   Med. 
Band  75,  p.  307.     1903. 

42  Streerath.     Archiv.  f.  Physiologie.     1910.     P.  295. 

43  Freund  and  Grafe.     Archiv.  f.  Escp.  Path.  u.  Phar- 
mahol.     Band  70,  page  135.     1912. 


44  ISAAC  OTT:  FEVER 

ments  upon  rabbits,  cutting  the  spinal  cord 
at  different  levels  and  studying  the  gaseous 
exchanges.  After  section  of  the  dorsal 
cord  the  physical  regulation  of  temperature 
was  interfered  with  and  the  heat  produc- 
tion was  increased.  In  section  of  the 
cervical  cord  at  7th  cervical,  the  heat  pro- 
duction was  normal,  but  the  x^hysical  and 
chemical  regulation  of  temperature  was 
disturbed. 

By  physical  regulation  is  meant  vaso- 
motor changes  and  the  evaporation  of 
sweat  and  the  water  from  the  lungs.  By 
chemical  regulation  is  understood  a  reflex 
from  the  skin  producing  increased  heat 
production,  increased  combustion  of  Rub- 
ner. 

Frank  and  Voit  ^^  have  shown  by  com- 
plete paralysis  of  the  body  in  curarization, 
that  the  chemical  regulation  of  the  body 
heat  is  not  lost. 

**  Frank  and  Voit.     Zeitschrift  f.  Biologic.     Band  24. 
N.  D. 


THERMOTAXIS  AND  METABOLISM     45 

Dr.  Robert  Meade  Smith  and  Dr.  Luk- 
janow,^^  in  Lndwig's  laboratory,  have 
studied  in  detail  tbe  fatigue  of  the  thermo- 
genic function  in  muscle,  and  also  the  law 
of  recovery,  with  and  without  blood  sup- 
ply. Each  mechanism  of  work  and  produc- 
tion of  heat  had  its  own  laws  as  regards, — 

(1)  the  influence  of  external  conditions; 

(2)  the  influence  of  fatigue ; 

(3)  the  influence  of  exhaustion; 

(4)  the  influence  of  temperature,  and 

(5)  the  effect  of  rest  and  of  circulating 
blood. 

As  Donald  MaoAlister  ^^  has  stated,  the 
contractile  material  in  muscle  is  not  the 
same  as  the  thermogenic.  The  thermo- 
genic is  exhausted  sooner  than  the  contrac- 
tile. Both  can  be  upbuilt  again  by  the  cir- 
culating blood,  but  the  contractile  in  some 
cases  sooner  than  the  thermogenic.     Both 

45  Du  Bois.-Reymond's  Archiv.     1880. 

46  "Nature  of  Fever."     1887. 


46  ISAAC  OTT:  FEVER 

metabolisms  are  affected  by  cold,  but  the 
thermogenic  much  sooner  and  much  more 
intensely  than  the  contractile.  There  is  no 
fixed  relation  between  the  laws  of  contrac- 
tion and  thermogenesis. 

Freund  and  Schlagintweit  ^"  found  as  a 
result  of  experiments  upon  rabbits  under 
curarin,  that  the  chemical  regulation  can 
functionate  without  motor  innervation  of 
the  muscles.  Their  experiments  confirm 
those  of  Sinelnikow 's,  that  during  curariza- 
tion  the  puncture  into  the  thermogenic  cen- 
ter elevates  the  temperature.  Infection 
could  not  produce  fever,  but  sodium  chlo- 
ride could  generate  it. 

Freund  ^^  after  section  of  vagi  on  the 
esophagus  beneath  the  diaphragm  in  rab- 
bits did  not  find  the  animals  quite  warm — 
their  temperature  stood  at  the  lowest 
normal  level.     The  animals  were  kept  in  a 

47  Freund  and  Schlao-intweit.  Archiv.  f.  Exp.  Patholo- 
gie  u.  Pharmak.     Band  71.     Heft  3  and  4.     P.  258. 

*8  Freund.  Archiv.  f.  Exp.  Pathol,  u.  Pharmakol. 
Band  72,  p.  295. 


TIIERMOTAXIS  AND  METABOLISM     47 

warm  room,  and  the  shaving  of  the  ab- 
domen may  have  been  one  of  the  causes  of 
low  temperature.  After  longer  observa- 
tion he  saw  no  disturbance  of  heat  regula- 
tion. The  animals  resisted  cold  and  heat 
by  their  temperature  regulation.  The 
same  was  true  when  he  cut  the  vagi  in  the 
neck  and  he  doubts  any  inhibitory  influence 
of  vagi  on  temperature,  as  held  by  Stefani 
and  Pari  and  also  by  Tscheschkow.  Fever 
could  also  be  produced  with  a  solution 
of  sodium  chloride  when  the  vagi  were 
cut. 

If  the  vagi  and  splanchnics  are  cut  the 
results  are  similar;  the  animals  can  also 
become  feverish  after  injection  of  sodium 
chloride  solution.  He  saw  no  marked  ac- 
tion by  vagi  on  chemical  regulation.  Sec- 
tion of  both  vagi  beneath  the  diaphragm, 
combined  with  the  high  dorsal  cord  section 
(above  the  6th  segment),  had  an  effect 
similar  to  that  of  the  dorsal  cord  section 
combined  with  extirpation  of  both  stellate 


48  ISAAC  OTT:  FEVER 

ganglia,  or  to  that  of  the  dorsal  cord  sec- 
tion combined  with  the  cutting  of  the  8th 
cervical  and  1st  dorsal  root.  The  animal 
had  no  heat  regulation  with  cold  or  heat, 
just  as  after  section  of  the  cervical  cord. 
After  these  combined  sections  experimental 
fever  could  not  be  produced. 

He  finds  it  difficult  to  see  an  antagonism 
between  the  sympathetic  and  para-sympa- 
thetic system  in  heat  phenomena.  He 
states  that  heat  regulation  is  in  some  way 
dependent  on  the  abdominal  organs. 

Ott  and  Scott  have  also  made  a  series  of 
experiments  upon  rabbits,  dividing  both 
the  right  vagus  and  right  sympathetic. 
The  cervical  sympathetic  was  also  excised 
from  the  clavicle  to  the  superior  cervical 
ganglion.  The  temperature  was  taken  in 
each  axilla  and  in  the  rectum  at  the  same 
hour,  at  intervals  of  about  two  days  for 
a  month.  It  was  always  found  that  the 
temperature  of  the  right  axilla  was  from 
0.46°    F.    to    0.8°    F.    higher    than    that 


THERMOTAXIS  AND  METABOLISM      49 

of  the  left.  Now  how  is  the  rise  of 
temperature  in  these  experiments  ex- 
plained? Temperature  is  maintained  by 
the  relation  between  thermogenesis  and 
thermolysis.  In  section  of  the  vagus 
and  sympathetic  we  have  destroyed  heat 
regulation.  The  question  arises,  how  has 
this  been  done?  Have  we  cut  vaso- 
motor fibers,  thus  producing  an  increased 
flow  of  blood,  which  would  cause  rise  of 
temperature?  Or  have  we  cut  an  afferent 
nerve  of  the  tuber  cinereum,  the  chief  regu- 
lating center,  which  cannot  through  its  ef- 
ferent nerves  in  the  vagus  and  sympathetic 
control  heat  regulation  in  the  right  anterior 
extremity.  If,  however,  we  take  those  ex- 
periments in  conjunction  with  those  of 
Freund,  Strassmann  and  Grafe  where  a 
section  of  the  vagi  beneath  the  diaphragm 
combined  with  section  of  the  spinal  cord 
about  the  upper  level  of  the  dorsal  region 
destroyed  chemical  regulation,  then  we 
should  infer  that  we  have  cut  some  of  the 


50  ISAAC  OTT:  FEVER 

heat  regulating  fibers  coming  from  the 
tuber  cinereum. 

Freund  *^  divided  the  upper  half  of  the 
cord  in  the  dorsal  region  of  the  rabbit  and 
found  that  heat  regulation  was  destroyed. 
He  then  punctured  the  corpus  striatum  and 
the  thalami.  He  found  that  section  of  the 
cord  up  to  2nd  dorsal  did  not  hinder  the 
hyperthermia  of  heat  puncture.  AVhen  the 
animals  become  poikilothermal,  then  even 
heat  punctures  were  without  effect. 

Freund  and  Marchand  ^'^  found  that  re- 
moval of  the  adrenals  caused  a  marked  fall 
of  temperature  and  a  diminution  of  sugar 
in  the  blood. 

Eimden,  Luthje  and  Liefman  ^^  have 
shown  that  in  the  dog  with  a  low  external 
temperature,  the  quantity  of  sugar  in  the 

49  Freund.     Archiv.    f.    Exp.    Pathol,    u.    Pharmakol. 
Band  72,  page  304. 

50  Freund  and  Marchand.  Archiv.  f.  Exp.  Pathol,  ii. 
Pharmakol.     Band  72,  page  56. 

51  Eimden.  Luthje  u.  Liefman.  Hofmeister  Beitrage, 
1907.     B.  10. 


TIIERMOTAXIS  AND  METABOLISM     51 

blood  is  regularly  considerably  higher ;  and 
Silberstein  ^^  has  shown  on  dogs  that  there 
is  a  very  close  relation  between  the  quan- 
tity of  sugar  in  the  blood,  the  external  tem- 
perature and  the  body  temperature.  In 
fever,  as  a  rule,  there  is  an  increase  in  the 
quantity  of  sugar  in  the  blood  increases. 

Freund  and  Schlagintweit  ^^  found  that 
section  of  the  dorsal  cord  below  the  5th  seg- 
ment leaves  the  sugar  puncture  active,  but 
if  you  cut  above  it  there  is  neither  gly- 
cosuria nor  hypergiycaemia  after  the  sugar 
puncture  or  injection  of  diuretin,  whilst 
adrenalin  produces  a  high  hypergiycaemia. 
The  section  of  the  dorsal  cord  up  to  its 
highest  segment  leaves  chemical  regulation 
intact,  which  is  seen  in  part  from  the  rise 
of  temperature  after  administration  of 
diuretin  and  adrenalin.  The  central  in- 
fluence upon  the  metabolism  of  the  carbo- 

52  Silberstein.     "Warmeregiilation  u.   ZuckerstoftVech- 
sel."     Kong  f.  inn.  Med.  Wiesbaden.     1913. 

53  Freund  and  Schlagintweit.     Archiv.  f.  Exp.  Path,  w, 
Pharmakol.     Band  76,  page  303. 


52  ISAAC  OTT:  FEVER 

hydrates  by  chemical  regulation  is  ex- 
cluded, since  the  section  of  the  splanchnics, 
as  well  as  section  of  the  dorsal  cord  above 
the  6th  segment  prevent  the  sugar  punc- 
ture effect  without  disturbing  heat  regula- 
tion. 

Nebelthan  ^^  found  that  section  of  the 
spinal  cord  in  the  rabbit  between  the  6tli 
and  7th  cervical  vertebrae  produced  a  fall 
of  temperature  and  that  infection  with  ery- 
sipelas of  the  pig  had  no  influence  on  tem- 
perature or  heat  production.  Here  the 
toxines  of  fever  act  upon  the  heat  regula- 
tion centers,  but  their  thermotaxic  fibers,  in 
great  part,  have  been  cut  off. 

If  the  mid-brain  is  severed  from  the 
medulla,  no  fever  can  be  produced,  accord- 
ing to  Sawadowsky.^^ 

That  thermotaxic  fibers  are  concerned  in 

54  Xebelthan.     Zeitschrift  f.  Biologic.     1899.     XXI,  p. 
353. 

55  Sawadowsky.     Centralhlatt    f.    Med.    Wissenschaft. 
1888.     Band  26,  p.  161. 


THERMOTAXIS  AND  METABOLISM     53 

chemical  regulation  of  heat  is  rendered 
probable  by  the  fact  that  section  at  the  7tli 
cervical  prevents  a  chemical  regulation. 
If  they  were  only  concerned  with  augment- 
ing or  decreasing  the  activity  of  the  ponto- 
bulbar centers  then  chemical  regulation 
should  continue.  It  is  very  probable  that 
about  the  7th  cervical  and  in  the  mid-brain 
fibers  run  which  are  concerned  in  thermo- 
taxis.  Their  pathway  is  probably  the  sym- 
pathetic and  the  vagus,  whilst  the  cord 
fibers  go  to  the  muscles,  and  others  enter 
the  sympathetic  ganglia  and  go  to  the  cells 
of  the  viscera. 

That  fibers  may  go  from  the  tuber  to  the 
thermolytic  centers  is  very  probable,  for  in 
the  tuber  is  a  vaso-tonic,  and  a  polypnoeic 
center  and  fibers  may  extend  to  the  sudor- 
ific centers.  This  is  the  heat  dissipation 
apparatus,  or  physical  regulation  of  heat. 
But  there  is  a  heat  producing  apparatus 
also  innervating  the  muscles  through  the 


54  ISAAC  OTT:  FEVER 

motor  nerves  and  the  viscera  by  the  sym- 
pathetic system.  This  is  the  chemical 
regulation  of  heat. 

I  see  no  reason  to  assume,  as  some  have 
done,  that  thermotaxic  nerves  do  not  run 
mainly  in  the  nerves  of  the  cerebro-spinal 
system  to  the  muscles,  but  rather  in  the 
sympathetic.  Certain  fibers  concerned 
with  the  production  of  heat  can  exist  in 
motor  nerves  whether  you  hold  that  heat 
puncture  can  succeed  or  not  in  a  curarized 
animal. 


LECTUEE  II 


LECTURE  II 

Gentlemen: — To-day    I    sliall    take    up 
lieat  dissipation  or  thermolysis. 

THERMOLYSIS 

This  is  carried  on  by  the  polypnceic  cen- 
ter in  the  tnber  cinerenm,  the  vaso-motor 
center,  and  the  sudorific  centers.  In  1891, 
I  ^  located  the  polypnceic  center  in  the 
tnber  cinerenm  which  drives  the  respira- 
tion center  to  increased  activity  and  thus 
throws  off  more  water  from  the  lungs. 

Nicolaides  of  Athens  -  has  made  several 
experiments  on  polypnoea,  and  in  1910  lo- 
cated its  center  in  the  corpora  striata.     I 

1  "Fever;  Thermotaxis  and  Calorimetry  of  Malarial 
Fever."  1889.  E.  D.  Vogel,  Eastoii,  Pa.  Also  "Mod- 
ern Antipyretics."  2nd  edition,  1892.  E.  D.  Vogel. 
Easton,  Pa. 

2  Nicolaides  u.  Dontas.  Archiv.  f.  Physiol.  191L 
H.  3  II.  4.     249. 

57 


^  ^ 
^  -o 

§ 

58 


TIIERMOTAXIS  AND  METABOLISM      59 

have  frequently  cut  away  the  corpora  stri- 
ata and  obtained  polypnoea.  The  center  is 
localized,  not  in  the  corpora  striata,  but  in 
the  tuber  cinereum.  His  statement,  that 
there  is  no  polypnoea  without  a  thermo- 
genic center,  I  can  fully  confirm,  but  the 
polypnoeic  center  is  in  the  tuber,  while  the 
thermogenic  centers  are  in  the  tuber  and 
the  corpus  striatum  and  of  these  the  tuber 
is  the  governing  thermogenic  center. 

Fig.  4.  Shows  the  effect  upon  rabbit 
when  the  corpora  striata  and  tuber  ciner- 
eum are  removed.  As  is  seen,  the  res- 
pirations decrease  instead  of  increasing, 
but  increase  somewhat  at  the  temperature 
of  105°  F.,  then  remain  about  the  same  in 
number  until  about  110°  F.,  when  they 
again  increase,  but  the  rate  never  rose 
above  the  normal  rate  before  heat  was  ap- 
plied. 

Fig.  5.  Shows  the  effect  of  a  weak 
faradic  current  applied  to  the  tuber 
cinereum.     When  the  base   of   the   brain 


60  ISAAC  OTT:  FEVER 

was  raised  at  its  anterior  part,  the  carotids 
being  ligated  during  the  elevation  of  the 
brain,  and  before  the  electric  irritation 
they  were  removed.  As  is  seen,  there  is 
a  great  increase  in  the  rate  of  respiration. 

Fig.  6.  Shows  the  arrest  of  respiration 
when  a  single  electric  shock  was  sent 
through  the  tuber,  with  arrest  of  the 
thorax  in  a  state  of  expiration.  The 
curves  are  to  be  read  from  right  to  left. 

Fig.  7.  Shows  the  rate  of  respiration 
and  the  temperature  curve  in  the  normal 
rabbit. 

That  a  polypnoeic  center  exists  in  man 
is  well  supported  by  a  case  of  Dr.  Jane- 
way's.  He  reports  a  hotel-keeper  who  in 
the  fall  of  1889  was  thrown  from  the  plat- 
form of  an  electric  car,  striking  the  pave- 
ment with  his  shoulders  and  the  back  of 
the  head.  In  consequence  of  this  fall,  he 
remained  unconscious  ten  days,  and,  when 
he  recovered  consciousness,  found  that  he 
was  breathing,  as  he  expresses  it,  *4ike  a 


I /W^Aa/\AA/i/v\Maaaaaaaa/\a^^^ 


Fig.  5. 

This  shows  the  effect  of  a  weak  faradic  current  to  the  tuber 
upon  the  rate  of  respiration. 


Fig.  G. 

This  shows  the  eifect  of  a  sing-le  electric  shock  to  the  tuber 
1  causing  expiratory  arrest. 


bo 


o 


a; 


62  ISAAC  OTT:  FEVER 

steam  engine  at  high  pressure."  He  has 
breathed  rapidly  ever  since,  and  in  1892 — 
in  February — the  rate  was  152  per  minute. 
Otherwise  he  was  in  good  health ;  the  heart, 
lungs  and  other  organs  were  healthy.  He 
had  a  tracheitis  due  to  the  rapid  respira- 
tion. This  case  turned  out  to  be  hysterical, 
although  the  functional  trouble  must  have 
been  connected  with  the  tuber,  for  no  one 
could  voluntarily  keep  up  so  rapid  a  rate. 

VASO-TONIC   ACTION    OF    TUBER    CINEREUM 

There  are  also  reasons  to  believe  that 
the  tuber  has  vaso-tonic  activity,  that  is, 
gives  tonus  to  the  vaso-motor  center. 

Fig.  8.  Shows  the  effect  of  puncture  of 
the  tuber.  The  arrow  represents  the  time 
of  the  lesion,  the  dotted  line  the  pulse,  and 
the  continuous  line  the  arterial  tension. 
The  tying  of  the  animal  did  not  cause  this 
fall,  as  the  effect  of  detention  does  not 
ensue  in  the  first  hour,  which  was  about  the 
time  the  observation  was  continued.     The 


Pulse  m  15  Seconas 


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Fig.  S. 
Effect  of  puncture  of  tuber  cinereum  upon  blood  pressure. 


63 


64  ISAAC  OTT  :  FEVER 

rate  or  the  depth  of  the  respirations  was 
not  perceptibly  altered  and  did  not  influ- 
ence the  arterial  tension. 

This  fall  ensued  invariably  in  six  experi- 
ments. These  observations  left  no  doubt 
in  my  mind  that  va so-tonic  centers  existed 
in  the  tuber  cinereum. 

SUDORIFIC    SECEETION 

The  sudorific  glands  are  under  the  con- 
trol of  the  sweat  centers  in  the  spinal  cord, 
whose  fibers,  I  have  shown,  run  down  the 
lateral  columns  of  the  cord.  The  evapo- 
ration of  water  from  the  skin  carries  away 
considerable  heat.  It  is  stated  that  a  man 
who  had  no  sweat  glands  by  hard  work 
sent  his  temperature  up  to  40-41°  C.  and 
his  respirations  became  rapid.  Dogs  who 
have  no  sweat  glands  cool  themselves  off 
by  polypnoea,  which  carries  off  the  water 
by  the  lungs  instead  of  by  the  skin.  The 
evaporation  of  a  liter  of  water  abstracts 
from  the  body  580  calories.     A  man  will 


THERMOTAXIS  AND  METABOLISM     65 

lose  daily  about  930  calories  by  evapora- 
tion (about  400  calories  from  the  water 
of  the  lungs  and  about  530  by  evaporation 
of  water  from  the  skin). 

Four-fifths  of  heat  dissipation  is 
through  the  skin,  and  the  quantity  of  heat 
dissipated  is  proportional  to  the  surface 
of  the  skin.  Kubner  measured  the  super- 
ficial area  of  the  body  and  calculated  the 
metabolism  per  square  meter  of  surface, 
which  he  calls  the  ^ '  surface  area  law. ' '  In 
adults,  resting,  Ekholm  found  it  to  be  44 
calories  per  square  meter  of  surface  per 
hour.  Hence  the  metabolism  of  an  animal 
varies  approximately  as  its  surface,  and 
not  as  its  mass.  The  relation  of  surface 
area  to  weight  is  much  larger  in  the  child 
than  in  the  adult,  and  the  heat  production 
is  proportionately  larger.  The  relation 
of  surface  radiation  to  the  development  of 
fever  explains  the  great  liability  of  a  child 
to  fever.  Disturbance  in  radiation  from 
his  large  surface  must  disproportionately 


66  ISAAC  OTT:  FEVER 

influence  the  body  temperature  when  com- 
pared with  the  relations  in  adults.  Con- 
sequently a  child  becomes  feverish  very 
easily,  and  also  becomes  chilled  very  easily. 
Also  the  heat  regulation  centers  are  not 
so  well  regulated  as  in  adults,  hence  chills 
and  fever  follow  each  other  rapidly  in 
children. 

Heat  regulation  by  the  heat  centers, 
mainly  the  tuber  cinereum  and  less  by  the 
corpus  striatum,  is  also  weakened  in  sleep ; 
hence  the  temperature  falls  from  this  cause 
and  lessened  production  of  heat  on  account 
of  the  muscular  inactivity.  Heat  regula- 
tion in  fever  is  also  weakened,  for  cold  ap- 
plications have  a  much  more  marked  effect 
in  reducing  temperature  than  they  do  in 
health. 

Dr.  Eugene  F.  DuBois,  with  a  Benedict 
calorimeter,  found  in  normal  controls  in 
man  an  average  production  of  34.4  calories 
per  hour  per  square  meter  of  the  body  sur- 
face. 


THERMOTAXIS  AND  METABOLISM      67 

Dr.  Eugene  F.  DuBois  of  the  Kussell 
Sage  Institute  of  Pathology,  in  Bellevue 
Hospital,  N.  Y.,  found  with  the  Benedict 
respiration  calorimeter  that  in  typhoid 
fever  the  heat  production  might  rise  from 
100  to  160  per  cent,  of  the  normal.  He  also 
found  that  at  this  stage  there  was  little  or 
no  specific  dynamic  action  manifested  by 
protein  or  carbo-hydrates,  that  is  to  say, 
the  taking  of  food,  even  in  large  quantities, 
did  not  increase  the  amount  of  heat  pro- 
duced. In  exophthalmic  goiter  the  total 
metabolism  might  rise  as  high  as  192  per 
cent,  of  the  normal  and  in  cretinism  it 
might  be  as  low  as  75  per  cent.  In  all  the 
various  diseases  studied  the  methods  of 
direct  and  indirect  calorimetry  agreed 
closely. 

INTERNAL.  SECRETIONS  AND  TEMPERATURE 

In  Basedow's  disease  heat  production 
is  increased,  probably  due  to  excessive  heat 
dissipation,  as  the  heart  is  weakened,  the 


68  ISAAC  OTT:  FEVER 

arterioles  are  dilated,  and  the  blood  ac- 
cumulating there  gives  off  a  considerable 
quantity  of  heat. 

Boldyreff  found  after  removal  of  the 
whole  thyroid  apparatus  in  cats  and  dogs 
that  there  was  a  loss  of  heat  regulation. 
After  elevation  of  temperature  clonic  con- 
vulsions ensued.  After  application  of  cold 
the  temperature  fell  and  the  convulsions 
ceased.  (Boldyreff.  Pflueger's  Archiv. 
Band  154,  page  470.) 

O.  Loewi  and  Weselko ''  found  no  influ- 
ence on  temperature  after  extirpation  of 
the  thyroid  in  rabbits.  Boldyreff  found 
after  extirpation  of  the  whole  thyroid  ap- 
paratus in  cats  and  dogs  that  it  was  very 
defective.  They  found  that  the  heat  punc- 
ture in  thyroidectomized  animals  was  al- 
ways followed  by  a  fall  of  temperature  in 
the  first  hour  instead  of  a  rise  as  in  normal 

3  Loewi     u.     Weselko.     Zentralhlatt     f.     Physiologie. 
1914.     No.  4,  page  197. 


THERMOTAXIS  AND  :\rETAB0LI8:\I      69 

animals.  Then  it  rose  at  best  only  1.3°, 
whilst  in  nonnal  animals  it  rose  2.5°  to  3°. 
Whilst  in  normal  animals  sugar  metabolism 
by  the  heart  at  the  temperature  increase 
was  greatly  increased,  but  in  thyroidec- 
tomized  animals  with  puncture  fever,  it  was 
the  same  as  in  animals  with  thyroidectomy 
alone. 

In  cretins  the  temperature  is  subnormal 
as  in  myxoedema,  and  thyroid  extract 
when  administered  raises  the  temperature. 

Infundibulin  (pituitrin)  (hypophysin  of 
Fuehner),  when  injected,  elevates  the  tem- 
perature. Gushing  found  that  when  the 
pituitary  was  removed  and  the  tempera- 
ture fell,  an  injection  of  the  anterior  part 
elevated  the  temperature  2-4°  C.  In  con- 
junction with  Dr.  Scott  I  have  seen  the 
temperature  fall  to  94°  F.  after  destruc- 
tion of  the  pars  anterior  in  a  monkey.  Ott 
and  Scott  found  that  large  doses  of  the 
parathyroid  lowered  the  temperature. 


70  ISAAC  OTT:  FEVER 

G.  Liljestrand  and  K.  Frumerie  ^  found 
the  normal  variations  of  temperature  in 
fasting  rabbits  are  much  smaller  than  in 
animals  with  the  usual  nourishment.  After 
splanchnicotomy  on  both  sides  we  have  an 
elevation  of  temperature.  The  heat  punc- 
ture in  the  corpus  striatum  succeeds  well 
— a  confirmation  of  the  observations  of 
Schultze  and  Elias.  After  extirpation  of 
the  solar  plexus  and  the  myenteric  plexus 
in  rabbit,  the  heat  puncture  is  as  effective 
as  before;  there  is  also  some  diarrhoea. 
After  partial  extirpation  of  the  adrenals 
the  effect  of  the  heat  puncture  is  weakened, 
— the  more  so,  the  greater  the  amount  of 
extirpation.  After  complete  removal  of 
the  adrenals  the  heat  puncture  does  not 
act.  After  extirpation  of  the  adrenals  in 
rabbits  there  is  often  a  diarrhoea. 

Doeblin  and  Fleischman  also  removed 
the  adrenals  in  three  rabbits.     In  two  the 

4  Skandinavisches  Archiv.  fur  Physiologie.     Band  130. 
4,  5  and  6  Heft.     P.  320.     1914. 


THERMOTAXIS  AND  METABOLISM     71 

temperature  fell  after  the  heat  puncture. 
In  the  third  animal  the  temperature  rose, 
but  the  presence  of  aberrant  adrenal  tis- 
sue was  not  excluded. 

In  two  rabbits  the  heat  puncture  was  ac- 
tive when  the  adrenal  was  separated  from 
the  central  nervous  system.  After  extir- 
pation of  the  solar  plexus  and  myenteric 
plexus  in  the  rabbit  the  heat  puncture  was 
active. 

But  the  Swedish  observers,  Liljestrand 
and  Frumerie,  made  many  more  experi- 
ments than  Doeblin  and  Fleischman,  and 
their  results  are  to  be  accepted  as  the  truth 
about  the  extirpation  of  adrenals  prevent- 
ing a  rise  of  temperature  after  puncture 
of  corpus  striatum. 

Ott  and  Scott  ^  found  in  the  rabbit  that 
the  repeated  injection  subcutaneously  of 
5  drops  of  adrenalin  elevated  the  tempera- 
ture from  103°  F  to  106.6°  F.,  a  rise  of  3.6°. 
This  was  not  due  to  more  oxygen  entering 

5  ott  and  Scott.     Medical  Bulletin.     1907. 


72  ISAAC  OTT:  FEVER 

the  lungs,  as  Gad's  aeroplethysmograpli 
showed  that  it  reduced  the  volume  of  air 
entering  the  lungs.  We  infer  it  stimulates 
the  thermogenic  centers,  because  after  cut- 
ting off  the  corpus  striatum  and  the  tuber, 
adrenalin  did  not  in  some  cases  cause  any 
rise  at  all,  the  rectal  temperature  remain- 
ing the  same.  This  rise  of  temperature 
was  not  due  to  diminished  dissipation  by 
vaso-constriction,  as  the  temperature  kept 
rising  an  hour  and  a  half  after  the  last  in- 
jection of  adrenalin  solution. 

The  fact  that  heat  puncture  does  not 
succeed  when  the  adrenals  are  removed 
lends  support  to  the  view  advanced  by  Ott 
and  Scott,  that  adrenalin  is  a  stimulant 
of  the  thermogenic  centers,  as  there  is  no 
rise  of  temperature  by  adrenalin  injections 
after  removal  of  the  tuber  cinereum.  It  is 
quite  probable  that  adrenalin  is  needed  to 
sensitize  the  endings  of  the  thermogenic 
nerves,  the  receptive  substance  of  cells,  so 
that  the  thermogenic  centers  can  act. 


TIIERMOTAXIS  AND  METABOLISM      73 

Crile  ^  has  shown  that  there  is  an  inter- 
dependence between  the  brain  and  the  ad- 
renals, that  the  brain  cells  (cerebellum  in 
his  experiments)  show  a  quantitive  rela- 
tion to  the  work  changes,  that  the  brain  is 
more  dependent  upon  the  adrenals  than  the 
adrenals  upon  the  brain,  that  the  brain  cells 
have  a  strong  affinity  for  adrenalin.  Mor- 
phine lessens  the  amount  of  adrenalin  in 
the  brain  cells.  After  excision  of  the  ad- 
renals there  is  a  progressive  loss  of  mus- 
cular power  and  a  diminution  of  the  body 
temperature.  Ott  and  Scott  have  shown 
that  foreign  proteids  injected  into  the  cir- 
culation increase  the  amount  of  adrenalin 
in  the  blood,  which  has  been  confirmed  by 
Crile.  The  fact  that  albumoses  and  pep- 
tones produce  an  increase  of  adrenalin  in 
the  blood  may  be  the  true  cause  of  the 
fever  in  this  case.  Crile  states  that  iodine 
aggravates  Graves'  disease  and  here  we 

6  Kinetic  System.     'New  York  State  Journal  of  Medi- 
cine, May,  1914.     Page  232. 


74  ISAAC  OTT:  FEVER 

have  an  increased  temperature.  lodotby- 
rin  and,  according  to  Crile,  thyroid  ex- 
tract in  large  doses  also  cause  fever;  and 
Ott  and  Scott  have  shown  that  iodothyrin, 
iodine  and  thyroid  extract  increase  the 
amount  of  adrenalin  in  the  blood,  con- 
firmed by  Gley,  as  shown  by  the  intestinal 
strip,  which  action  of  adrenalin  on  the  in- 
testine in  causing  it  to  stop  all  its  peris- 
taltic movements  and  relax  was  shown  by 
Ott  ^  in  1886.  In  myxoedema  we  have  sub- 
normal temperatures.  In  Addison's  dis- 
ease, where  adrenalin  is  deficient,  there  is 
also  a  subnormal  temperature.  Morphine 
diminishes  the  temperature  and  according 
to  Crile  diminishes  the  amount  of  adrena- 
lin in  the  blood,  and  this  lack  of  adrenalin 
may  be  one  of  the  causes  of  the  decrease  of 
temperature  by  morphine. 

From  all  these  facts  I  infer  that  adren- 
alin has  a  very  potent  activity  in  the  in- 

7  Medical  Bulletin.     1886. 


THERMOTAXIS  AND  METABOLISM      75 

crease  of  temperature  when  it  is  in  excess 
in  the  blood. 

> 

IS    FEVER   BENEiFICIAL? 

Crile  holds  that  the  fever  may  be  so  fierce 
in  the  destruction  of  bacteria  that  the  body 
itself  may  undergo  dissolution. 

Adrenalin.  Crile  states  that  it  causes 
hyperchromatism  followed  by  chromatoly- 
sis  and  in  over-doses  destroys  the  cells  of 
the  cerebellum.  When  the  adrenals  are 
excised  the  Nissl  substance  disappears  in 
a  progressive  manner  up  to  death.  Ad- 
renalin excites  the  brain  and  causes  the 
brain  to  convert  latent  energy  into  heat 
and  motion. 

Morphine.  Crile  found  that  under  large 
doses  of  morphine  the  changes  due  to  toxin 
of  the  brain  cells  were  largely  prevented. 
Thyroid  and  iodine  have  the  same  effect 
as  infection  and  muscular  exertion  in  the 
production    of    fever    and    of    brain    cell 


76  ISAAC  OTT:  FEVER 

changes.  This  is  evidence,  according  to 
Crile,  that  certain  constitutents  of  the 
brain  cells  are  conserved  in  the  work  per- 
formed by  the  brain  in  the  production  of 
fever. 

Fear  causes  fever  in  animals  and  Can- 
non has  shown  that  it  gives  rise  to  the  pro- 
duction of  more  adrenalin,  which  is  one  of 
the  causes,  here,  of  fever.  Anxiety  also 
causes  fever,  probably  by  excess  of  adren- 
alin in  the  blood.  Crile  observed  an  aver- 
age rise  of  temperature,  1%°  F.,  in  a  ward 
of  children  as  a  result  of  a  Fourth  of  July 
celebration. 

Crile  found  by  the  intestinal  strip  test 
that  fear,  rage,  anaphylaxis  after  indol- 
skatol,  leucine  and  tyrosin  and  the  toxins 
of  diphtheria,  of  colon  bacillus,  toxins  of 
streptococcus,  staphylococcus,  foreign  pro- 
teids  and  strychnia  increase  the  adrena- 
lin in  the  blood.  The  test  was  negative 
after  thyroid  extract,  anesthesia  and 
trauma  and  after  the  injection  of  the  juices 


THERMOTAXIS  AND  METABOLISM     77 

of  the  various  organs  of  the  same  animal. 
Placental  extract  gave  a  positive  reac- 
tion. After  section  of  the  splanchnics,  the 
positive  test  by  the  above  mentioned  arti- 
cles became  negative.  Deep  morphiniza- 
tion  prevented  positive  results  by  the  fore- 
going adequate  agents.  In  brief,  all  the 
agents  which  cause  hyperchromatism  and 
chromatolysis  gave  positive  results  for  ad- 
renalin. The  one  agent  which  protected 
the  brain  cells'  Nissl  substance  was  mor- 
phine. H-ion  concentration  test  showed 
that  all  of  the  adequate  stimuli  giving  a 
positive  result  in  the  intestinal  strip  test 
showed  a  diminution  of  the  acidity  of  the 
blood  from  the  adrenal  vein.  Alkalies 
cause  histological  changes  in  adrenals; 
acids  do  not.  The  adrenals  activate  the 
brain;  the  brain  also  activates  the  adren- 
als. Crile  believes  that  the  Nissl  substance 
is  a  volatile,  unstable  combination  of  cer- 
tain elements  of  the  brain  cells  and  ad- 
renalin, because  the  brain  deprived  of  ad- 


78  ISAAC  OTT  :  FEVER 

renalin  does  not  take  the  Nissl  stain  and 
the  adrenals  alone  do  not  take  the  Nissl 
stain. 

Morphine  and  nitrous  oxide  prevent  the 
consumption  of  the  Nissl  substance,  prob- 
ably by  preventing  the  oxidation  of  the 
brain.  A  combination  of  adrenalin,  oxy- 
gen and  certain  brain  cell  constituents 
causes  electric  discharge  that  produces 
heat  and  motion.  All  of  the  adequate  stim- 
uli with  the  intestinal  strip  reaction,  after 
prolonged  insomnia  which  affected  the 
brain  and  the  adrenal  tissues  also  pro- 
duced identical  histological  changes  in  the 
liver  cells.  Hence  Crile  infers  that  the 
brain,  adrenals  and  liver  are  mutually  de- 
pendent upon  one  another  for  the  conver- 
sion of  latent  into  kinetic  energy  of  heat 
and  motion.  In  the  rabbit  insomnia  of  a 
hundred  hours  exhausted  some  of  the  rab- 
bits and  killed  others.  On  post  mortem 
and  histological  studies  of  all  the  tissues 
and  organs  of  the  body,  there  were  marked 


THERMOTAXIS  AND  METABOLISM     79 

histological  changes  in  only  three  organs 
— the  liver,  the  brain  and  the  adrenals. 
These  bear  the  stress  of  life;  the  brain  is 
the  battery,  the  adrenals  the  oxidizer  and 
the  liver  the  gasoline  tank  and  the  muscles 
the  furnace.  The  thyroid  is  the  pace 
maker;  it  regulates  the  rate  of  discharge 
of  energy. 

Crile  states  that  in  Graves'  disease  we 
find  an  extraordinary  degree  of  exaggera- 
tion of  the  whole  action  of  the  kinetic  mech- 
anism. Emotion,  pain  and  infection  pro- 
duce an  exaggeration  of  the  conversion  of 
energy.  In  acute  Graves'  disease  the  ex- 
plosive conversion  of  latent  energy  into 
heat  and  motion  is  unequaled  in  any  other 
disease.  Feeding  thyroid  produces  all  the 
phenomena  of  Graves'  disease  except  ex- 
ophthalmus  and  the  emotional  facies. 
Excessive  doses  of  iodine  alone  cause  most 
of  the  symptoms  of  Graves'  disease. 
Hence  by  normal,  excessive,  or  subnormal 
secretion  of  the  thyroid  we  produce  nor- 


80  ISAAC  OTT:  FEVER 

mal,  adynamic  and  an  excessively  dynamic 
state.  Defective  action  by  the  organs  in 
the  kinetic  chain  causes  loss  of  heat,  loss 
of  muscular  and  emotional  action  and  the 
power  of  combating  infection. 

Overwhelming  action  of  the  kinetic  sys- 
tem produces  shock.  The  essential  path- 
ology of  shock  is  identical  with  its  cause. 
Crile  states  if  the  brain  can  not  endure 
the  strain  we  have  neurasthenia;  if  the 
thyroid  can  not  endure  the  strain  we 
have  enlargement  of  it  or  Graves' 
disease  or  colloid  goitre.  If  the  ad- 
renals can  not  stand  the  strain  we 
have  cardio-vascular  disease.  If  the  liver 
can  not  endure  the  strain  we  have  acidosis. 
If  the  liver's  neutralizing  effect  is  only  par- 
tially lost,  then  the  acidity  may  cause 
Bright 's  disease.  Excessive  activity  of  the 
kinetic  system  may  cause  glycosuria  and 
diabetes.  Emotional  strain,  pregnancy, 
stress  of  business  or  professional  life  are 
all  activators  of  the  kinetic  system.    Hence 


THERMOTAXIS  AND  METABOLISM      81 

we  can  understand  how  emotions,  acute  or 
clironic  infections  may  cause  either  Graves' 
disease  or  cardio-vascular  disease;  how 
chronic  intestinal  stasis  with  the  resultant 
absorption  of  toxins  causes  cardio-vascular 
disease,  neurasthenia  or  goiter.  It  also 
affords  an  explanation  of  phenomena  of 
shock,  whatever  the  cause, — toxins,  infec- 
tions or  foreign  proteids,  anaphylaxis, 
psychic  stimuli  or  a  surgical  operation. 
The  idea  of  the  kinetic  system  has  made 
possible  the  shockless  operation,  it  has  ex- 
plained the  cause  and  treatment  of  Graves ' 
disease  and  the  control  of  shock  and  acute 
infection  by  overwhelming  morphinization. 

HYPEKTHERMIA 

Pathologists  for  more  than  a  hundred 
years  have  held  that  hyperthermia  in  fever 
was  due  to  an  increased  production  of 
heat.  Virchow  ^  by  a  study  of  the  metab- 
olism in  fevers  proved  a  greater  intensity 

8  Virchow.     "Path.  u.  Tlier."  1,  1854, 


82  ISAAC  OTT:  FEVER 

than  in  normal  conditions,  and  that  it  was 
the  cause  of  the  hyperthermia. 

Traube  ^  was  the  first  to  put  forth  the 
theory  that  hyperthermia  was  due  to  de- 
creased dissipation  of  heat  from  constric- 
tion of  the  arterioles  due  to  the  action  of 
the  toxines,  and  not  to  an  increased  pro- 
duction of  heat.  But  Tscheschichin,  Auer- 
bach,  Wachsmuth  combatted  this  view  of 
Traube 's. 

According  to  Liebermeister  ^^  the  hyper- 
thermia is  due,  partly  to  an  increased  pro- 
duction of  heat,  but  especially  to  a  change 
in  the  heat  regulation  apparatus.  Ley- 
den  ^^  also  supported  Liebermeister  in  this 
view. 

Senator  ^^  then  made  some  experiments 
and  supported  Traube  in  his  view  that  the 

9  Traube.  "Beitrage  z.  Chem.  Physiol,  u.  Pathol."  2 
and  3.     Allg.  Med.  Centralztg.     1863-1864. 

loHandb.  d.  "Pathol,  ii.  Ther.  des  Fiebers."  Leip- 
zig, 1875. 

n  Leydeii.     Deutsch.  Archiv.  f.  Klin.  Med.     536.     1869. 

12  "Untersuch  ucber  den  fieberhaften  Prozess."     1873. 


THERMOTAXIS  AND  METABOLISM      83 

most  important  factor  in  hyperthermia  was 
the  retention  of  heat,  especially  caused  by 
the  tetanic  contraction  of  the  peripheral 
vessels.  Senator,  however,  believed  that 
there  was  also  an  exaggeration  of  heat  pro- 
duction, due  to  an  increase  in  the  combus- 
tion of  the  proteins,  whilst  the  combustion 
of  the  carbohydrates  and  fats  did  not 
change  much. 

Then  we  have  the  theory  of  Murri  ^^  that 
fever  is  not  produced  by  retention  of  heat 
but  by  an  increase  of  thermogenesis,  due 
to  a  direct  action  of  pyretogenic  substances 
upon  the  cells  of  the  organism  independent 
of  the  nervous  system.  These  are  the 
principal  theories  of  the  second  half  of  the 
nineteenth  century. 

Babak  ^^  holds  that  the  heat  production 
in  fever  is  slightly  diminished.  Such  are 
the  principal  views  of  many  observers,  but 

13  Murri.     "Del    Potere    regolatore    della    temperature 
animale."     Fireiize,  1873. 

14  Babak.  ''Ueber  die  Waernieregulation  ini  Fieber." 
Archil',  f.  d.  gcs.  Physiologic.     102,  320.     1904. 


84  ISAAC  OTT:  FEVER 

the  mass  of  testimony  shows  that  there  is 
an  increased  production  of  heat  in  fever, 
and  afterwards  that  the  heat  regulation 
apparatus  is  reset  at  a  higher  figure,  as 
Liebermeister  taught. 

Porcelli-Titone  ^^  has  made  experiments 
on  rabbits  with  a  water  calorimeter.  He 
produced  fever  with 

(1)  The  nucleo-proteid  of  plague  bacil- 
lus; 

(2)  Toxine  of  colon  bacillus; 

(3)  Toxine  of  streptococcus; 

(4)  Nucleo-proteid   of   streptococcus; 

(5)  Nucleo-proteid  of  typhus  bacillus; 

(6)  Toxine  of  diphtheria; 

(7)  0.85  per  cent,  sodium  chloride  solu- 
tion. 

He  injected  these  substances  into  a  vein 
in  the  ear.  In  the  cat  he  used  the  nucleo- 
proteid  of  the  plague  bacillus  and  toxine 
of  colon  bacillus,  whilst  in  the  dog  he  used 

15  Porcelli-Titone.     "Bioclieniische    zeitschrift."     Band 
58,  page  30.5.     1914. 


THERMOTAXIS  AND  METABOLISM     85 

the  streptococcus  and  the  plague  bacillus. 
He  used  an  electric  motor  to  run  the  agi- 
tator to  mingle  the  water,  a  method  first 
used  in  the  Ott  calorimeter,  in  1892.  The 
error  of  the  instrument  of  Titone  was  0.1 
calorie.  The  error  of  Ott's  little  calori- 
meter for  animals  is  5.4  per  cent,  when 
tested  by  burning  absolute  alcohol. 

Titone 's  results  were  as  follows :  The 
heat  balance  during  the  beginning  of  a 
fever  is  different,  according  to  the  pyreto- 
genic  agent.  It  depends  not  only  on  the 
fever  producing  agent  but  also  upon  the 
kind  of  animal.  In  rabbits  there  is  a  great 
increase  of  heat  production  by  the  action 
of  nucleo-proteids,  and  typhus  bacillus  and 
a  small  increase  by  action  of  sodium  chlo- 
ride solution  and  the  toxines  of  colon  bacil- 
lus; no  temperature  changes  ensued  from 
the  diphtheria  toxine.  The  nucleo-proteid 
of  streptococcus  and  still  more  the  plague 
bacillus  lowered  thermogenesis. 

In   dogs   the   nucleo-proteid   of   plague 


86  ISAAC  OTT:  FEVER 

bacillus  caused  a  slight  increase  in  heat 
production,  while  the  streptococcus  pro- 
duced a  great  increase. 

In  cats  the  nucleo-proteid  of  the  plague 
bacillus  lowered  heat  production,  while  the 
toxine  of  the  colon  bacillus  caused  a 
marked  increase. 

The  estimations  of  the  Coo  eliminated 
confirmed  the  direct  calorimetric  data. 

As  hyperthermia  can  be  called  out  when 
the  heat  production  is  diminished  (at  times 
20^)  and  in  other  cases  where  the  heat 
production  is  increased  (but  generally  not 
beyond  the  physiological  variations)  it 
shows  that  there  is  no  constant  quantitive 
relation  of  heat  production  to  the  elevation 
of  temperature.  Hence  Titone's  hypothe- 
sis is  that  the  greatest  factor  in  the  hyper- 
thermia of  fever  is  diminished  heat  dissi- 
pation. From  these  data  it  is  probable, 
he  states,  that  the  pyretogenic  agent  calls 
up  hyperthermia  by  an  action  upon  the 
heat  regulation  mechanism  for  dissipation 


THERMOTAXIS  AND  METABOLISM      87 

of  heat,  and  that  this  is  independent  of  the 
action  upon  the  thermogenic  apparatus. 
He  believes  that  his  experiments  showed 
that  the  different  results  obtained  by  va- 
rious observers  were  due  to  different  types 
of  fever  studied,  and  the  different  kinds 
of  animals  used. 

As  to  the  last  mentioned  view,  /  might 
state,  in  man  we  have  an  increase  of  gas- 
eous exchange  in  fever  (Leyden,  Lieber- 
meister,  Eegnar,  Loewi,  Kraus  and 
Chvostek,  Kiethus),  or  a  decrease  of  gas- 
eous exchange  (Wertheim,  Grehant  and 
Quinqaud,  Riethus).  While  the  majority 
of  observers  on  man  with  a  calorimeter 
found  an  increase  of  heat  production 
(Liebermeister,  Wahl,  Hattwich,  Chesno- 
coff,  Leyden,  Langlois),  others  found,  like 
Traube,  a  diminished  dissipation  (C. 
Rosenthal,  Maragliano,  T.  Rosenthal). 
Here  the  same  animal  was  used,  yet  dif- 
ferent results  were  obtained. 

Temperature    is    the    relation    between 


88  ISAAC  OTT:  FEVER 

heat  production  and  heat  dissipation,  and 
while  high  temperature  is  usually  caused 
by  increased  production  of  heat,  it  can 
also  be  the  result  of  a  diminished  produc- 
tion with  a  diminished  dissipation,  as  I 
have  found  pretty  frequently  in  my  calori- 
metrical  work. 

The  animal  may  start  with  a  normal  heat 
production  and  heat  dissipation,  and  the 
regulation  be  set  lower  instead  of  higher 
to  produce  a  high  temperature.  It  is  quite 
probable  that  these  exceptional  cases  are 
explanatory  of  some  of  the  discordant  re- 
sults, and  not  the  variety  of  animal  or 
the  different  toxines  used,  as  held  by 
Titone. 

The  amount  of  C02  follows  heat  produc- 
tion, according  to  Titone,  and  if  so,  tlie 
discordant  results  in  gaseous  exchanges 
can  be  explained  in  the  manner  just  men- 
tioned. 

As  to  the  afebrile  causes  of  typhoid 
fever,  the  setting  of  the  heat  regulation 


THERMOTAXIS  AND  METABOLISM      89 

apparatus  at  a  lower  level  explains  them 
also. 

HEAT  PRODUOTION   IN   NORMAL.  AND   HYPER- 
THERMIC   CONDITIONS 

Dr.  Wm.  A.  Carter  made  a  series  of  ex- 
periments upon  rabbits,  cats  and  dogs  in 
my  laboratory,  showing  the  heat  produc- 
tion and  heat  dissipation  during  twenty- 
four  hours,  the  animal  being  in  a  state  of 
hunger  for  three  days.  Out  of  twenty 
days  the  maximum  heat  production  came 
at  7  A.  M.  three  times,  at  11  a.  m.  twice,  at 
3  p.  M.  five  times,  at  7  p.  m.  three  times,  at 
11  p.  M.  four  times  and  at  3  a.m.  three 
times,  or  ten  times  during  the  day  and  ten 
times  at  night.  In  experiments  in  which 
the  same  animal  was  used  the  maximum 
and  minimum  of  heat  production  did  not 
appear  twice  at  the  same  time.  There  was 
no  diurnal  rhythm  of  heat  production  and 
of  heat  dissipation.  There  was  the  usual 
diurnal  rise  of  temperature  in  the  evening 


90  ISAAC  OTT:  FEVER 

(7  P.  M.  to  11  p.  M.)  and  the  minimum  morn- 
ing temperature  (7  a.m.  to  11  a.m.),  the 
same  as  has  been  found  in  man. 

In  another  series  of  experiments  Carter 
used  hungry  animals,  and  the  cruciate  cen- 
ter of  Eulenburg  and  Landois  was  de- 
stroyed, which  developed  a  hyperthermia. 
The  results  showed  a  much  greater  varia- 
tion in  temperature  in  the  animal  with  hy- 
perthermia when  compared  with  the  nor- 
mal animal.  Here  it  was  found  that  heat 
production  and  temperature  were  entirely 
independent  of  each  other.  We  give  in 
Figs.  9  and  10  two  composite  curves  show- 
ing the  average  heat  production,  heat  dis- 
sipation and  rectal  temperature.  The  con- 
tinuous line  represents  heat  production, 
the  dotted  line  heat  dissipation,  and  the 
line  below  shows  the  rectal  temperature. 

PROF,   wood's  BXPEEIMENTS 

The  chief  work  on  artificial  fever  in  this 
country  has  been  done  upon  dogs  by  Prof. 


Fig.  9. 

Composite  curve  showing  the  average  of  20  experiments 

upon  starved  animals. 


Fig.  10. 

Composite  curve  showing  the  average  of  12  experiments 

upon  fevered  animals. 

91 


92  ISAAC  OTT:  FEVER 

H.  C.  Wood  (Sr.)  in  his  laboratory.^^  It 
was  upon  the  heat  production  and  heat  dis- 
sipation in  animals  made  feverish  by  the 
injection  of  putrid  blood.  He  also  studied 
pepsin  fever  in  conjunction  with  Drs. 
Eeichert  and  Hare. 

Tabulation  of  Prof.  Wood's  results  gives 
the  following  results : 

+  means  increased  H.  P.,  —  decreased 
H.  P.,  compared  with  the  second  day. 

H.  P.  1st  fever  day.     H.  P.  2d  fever  day. 


Exp.  110 

+  26 

+  31 

''  111 

+  2 

+  5 

"      112 

6 

+  8 

''      113 

3 

+  18 

''   114 

+  37 

"     116 

+  3 

An  examination  of  Professor  Wood's  re- 
sults show  on  the  first  fever  day  an  in- 
crease of  H.  P.  in  three  experiments,  and 

16  Wood.  "Fever,"  1880.  Smithsonian  Contributions 
to  Knowledge.  No.  357.  "Fever  Thermotaxis  and  Cal- 
orimetry."     1889.     E.  D.  Vogel,  Easton,  Pa. 


THERMOTAXIS  AND  METABOLISM     93 

a  decrease  of  H.  P.  in  two.  On  second 
fever  day  there  is  an  increase  in  five  ex- 
periments. 

These  increments  are  much  greater  than 
those  found  by  me,  and  are  partly  due  to 
observations  made  at  dissimilar  parts  of 
the  day  without  regard  to  the  diurnal 
rhythm. 

My  experiments  upon  fever  were  made  in 
1889  upon  rabbits  and  cats  deprived  of 
food  for  twelve  hours  before  any  observa- 
tions were  made.  They  were  carried  on 
for  seventy-two  hours. 

The  access  of  fever  was  studied  during 
the  first  three  hours  and  at  intervals  after- 
ward. It  showed  that  after  injection  per 
jugular  of  two  drops  of  putrid  blood,  the 
heat  production  rises  rapidly  and  becomes 
greatest  some  hours  before  the  fever  curve 
attains  its  height.  At  the  same  time  the 
curve  of  H.  D.  is  lagging  behind  the  curve 
of  H.  P.,  although  following  it  in  its  up- 
ward   ascent.     After    a    while    the    H.  P. 


94  ISAAC  OTT:  FEVER 

curve  falls  temporarily  beueath  the  curve 
of  H.  D.  and  the  temperature  curve  falls. 
It  will  be  seen  normally  and  during  the 
fever  in  the  curve  of  H.  P.  that  it  exhibits 
fluctuations,  a  fact  pointed  out  by  Senator. 
The  fluctuations  of  H.  P.  are  greater  in 
fever.  I  believe  the  fluctuations  are  due 
to  the  action  of  external  agencies  upon  the 
thermotaxic,  thermogenetic  and  thermoly- 
tic  apparatus,  which  are  playing  at  see- 
saw, at  one  time  making  H.  P.,  greater  than 
H.  D.,  at  another  making  H.  D.  greater 
than  H.  P. 

In  Exp.  1  there  is  an  illustration  of  a 
high  temperature,  although  H.  P.  and  H.  D. 
have  fallen  below  normal  of  the  hunger 
day  or  second  day.  In  Exp.  4,  we  see  that 
during  three-fourths  of  the  last  fever  day 
the  temperature  is  below  normal,  and  at 
the  last  observation  H.  P.  is  five  units 
greater  than  those  of  same  period  on  hun- 
ger day.  Tlie  ((uestion  arises  how  is  Exp. 
1  to  be  explained? 


THERMOTAXIS  AND  METABOLISM     95 

Dr.  Donald  MacAlister  ^'  has  given  the 
following  explanation.  Suppose  a  tall 
vessel  containing  water,  the  level  of  the 
water  representing  temperature.  Let  two 
pipes  be  connected  with  this  vessel,  one 
conveying  water,  the  other  carrying  it  off. 
Let  the  inlet  and  exit  tubes  be  each  pro- 
vided with  a  stop-cock,  and  let  the  two  stop- 
cocks be  connected  by  a  rigid  link  which 
insures  that  they  always  turn  together  and 
by  the  same  amount.  If  to  start  with,  the 
inflow  and  outflow  are  equal,  then  however 
I  move  the  linked  stop-cocks,  the  height  of 
the  water  will  be  the  same.  Now  remove 
the  rigid  link  and  connect  the  stop-cocks 
by  a  spiral  spring.  If  now  you  move  the 
inflow  stop-cock  so  as  to  increase  the  flow, 
the  outflow  one  will  not  at  once  follow,  and, 
the  balance  being  broken,  the  level  of  water 
will  rise.  But  shortly  the  elasticity  of  the 
spring  comes  into  activity,  the  outflow  is 

1-  '-Fever  Tliermotaxis  and  Calorimetry."  1889.  E. 
D.  Yogel,  Easton,  Pa. 


96  ISAAC  OTT:  FEVER 

equal  to  the  inflow  and  the  rise  will  cease, 
but  the  new  high  level  will  be  maintained. 
Everj^  movement  of  either  stop-cock  will 
affect  the  level,  which  will  fluctuate  ac- 
cordingly, but  its  height  at  any  moment 
will  not  be  an  index  of  the  amount  of  in- 
flow at  that  moment.  The  inflow  may  be 
slight  while  the  level  is  high.  If  now  you 
substitute  H.  P.  for  inflow  and  H.  D.  for 
outflow,  and  the  rigid  link  represents  the 
healthy  thermotaxic  mechanism,  then  when 
this  is  weakened  or  relaxed  or  broken  the 
steadiness  of  the  normal  level  is  impos- 
sible. 

PEOTEIN    FEVER 

Ott  and  Collmar  ^^  studied  the  effect  of 
albumoses  and  peptones  upon  animals. 
We  discovered,  in  1887,  that  they  produced 
fever.  The  albumoses  and  peptones  were 
prepared  from  egg  albumen  by  Professor 

1^  ott  and  Collmar.     Journal  of  PhysioJogy,  Vol.  VIIT, 
p.  218.     18S7. 


THERMOTAXIS  AND  METABOLISM     97 

Chittenden  of  Yale  and  were  injected  per 
jugular.  We  made  experiments  upon  rab- 
bits and  found  that  both  albumoses  and 
peptones  produced  fever  by  an  increased 
production  of  heat,  but  during  the  first 
hour  the  heat  production  is  decreased  by 
the  peptones,  whilst  the  albumoses  in- 
creased it  during  the  first  hour.  Both  usu- 
ally decreased  heat  dissipation  during  the 
first  hour,  which  then  rose  with  the  in- 
creased production.  Krehl  and  Matthes,^^ 
in  1895,  confirmed  these  facts.  Vaughn,^*^ 
in  1909,  demonstrated  it  also  by  the  admin- 
istration of  foreign  protein  parenterally. 

FEVEK   IN    MAN 

Calorimetry  of  Malarial  Fever.  In  my 
experiments  it  was  brought  out  for  the 
first  time  that  in  septic  fever  the  heat 
production  and  heat  dissipation  may  be 

19  Krehl  and  Matthes.     Archiv.  f.  exp.  Path.  u.  Pharm. 
1895,  XXXV.     232. 

20  Vaughn.     "Protein  Split  Products."     P.  372.     1914. 


98  ISAAC  OTT:  FEVER 

diminislied  during  the  whole  course  of  the 
fever.  Usually  septic  fever  in  its  in- 
itial stage  is  accompanied  by  an  increased 
production  of  heat.  Now  it  is  easy  to  defi- 
nitely settle  the  question  as  to  the  increase 
or  decrease  of  heat  production  in  fever, 
and  I  have  studied  the  calorimetry  of  ma- 
larial paroxysms  during  the  cold,  hot,  and 
sweating  stages.  The  instrument  which 
I  have  designed  is  constructed  as  follows : 
It  is  composed  of  two  cylinders  of  gal- 
vanized iron — one  smaller  than  the  other 
and  enclosed  with  it  (Fig.  11).  The  space 
in  which  the  man  lies  upon  a  mattress  is 
six  feet  long  and  two  feet  in  diameter. 
Air  is  conveyed  to  him  through  the  tube 
H  (to  which  is  attached  at  its  inner  end  a 
coiled  leaden  tube  through  which  the  air 
enters  the  instrument),  and  traverses  the 
whole  length  of  the  apparatus  and  enters 
the  hollow  tube  of  lead  at  P,  and  finally 
emerges  at  B,  having  given  off  its  heat  to 
the  water  between  the  two  cylinders.     The 


6    S 


100  ISAAC  OTT:  FEVER 

meter,  M,  is  run  by  the  water-wheel,  N, 
which  aspirates  the  water  through  the 
whole  apparatus  by  means  of  a  hose,  E, 
connecting  it  with  the  lead  tube  at  B.  The 
space  between  the  cylinders  is  filled  with 
about  four  hundred  and  eighty-four  pounds 
of  water.  This  water  is  kept  thoroughly 
mixed  by  means  of  the  agitator,  0,  which 
has  two  arms.  These  arms  are  pushing 
the  water  back  and  forth  thirty  times  a 
minute,  the  motion  being  caused  by  water 
running  the  motor,  X,  which,  by  means  of 
the  wheel,  Z,  and  the  eccentric,  drives  the 
agitator.  The  thermometer.  A,  gives  the 
temperature  of  the  water,  and  on  account 
of  the  thorough  mixing  of  the  water  by  the 
agitator,  gives  the  accurate  record  of  the 
temperature  of  the  water  throughout  the 
apparatus.  The  thermometer  is  pushed 
farther  down  than  is  represented  in  the  fig- 
ure; it  usually  lies  aside  of  the  tube  H. 
The  air-tube,  B,  also  has  a  thermometer 
to  denote  the  temperature  of  the  air  as  it 


THERMOTAXIS  AND  METABOLISM     101 

is  heated  up  by  the  man.  The  thermom- 
eter at  B  is  graduated  into  tenths,  while 
the  thermometer  at  A  is  graduated  into 
fiftieths,  but  they  are  so  far  apart  that  one 
one-hundredth  of  a  degree  Fahrenheit  can 
be  read.  The  temperature  of  the  mouth 
was  taken  by  a  thermometer  giving  tenths, 
but  I  expect  to  use  one  so  graduated  that 
I  can  read  fiftieths.  The  rectal  tempera- 
ture would  have  been  preferable  on  account 
of  accuracy.  The  bucket,  I,  receives  the 
water  from  the  motor,  X,  and  so  conveys 
it  to  the  water-wheel,  N,  that  it  runs  the 
meter  as  an  aspirator.  The  meter  is  filled 
with  water,  and  belongs  to  Voit's  little  res- 
piration  apparatus.  The  quantity  of  air 
aspired  an  hour  is  five  to  six  thousand 
liters,  which  is  sufficient  for  respiratory 
purposes.  The  instrument  is  made  air- 
tight by  means  of  the  door,  K,  which  is 
clamped  by  eight  powerful  iron  clamps. 
The  inner  edge  of  the  door  is  lined  with 
rubber.     The  whole  apparatus  is  enclosed 


102  ISAAC  OTT:  FEVER 

in  over  six  inches  of  saw-dust,  the  door, 
K,  having  against  it  a  saw-dnst  mattress. 
The  interior  of  the  instrument  is  lighted  by 
an  electric  light  of  one-candle  power,  by 
which  a  paper  can  be  read. 

With  these  arrangements,  excepting 
light,  and  a  mattress  inside  the  instrument 
I  have  tested  the  apparatus.  As  the  ap- 
paratus necessary  for  the  hydrogen  test 
was  not  available,  I  used  absolute  alcohol. 
The  different  physicists  who  have  burned 
a  gramme  of  alcohol  have  obtained  the  fol- 
lowing various  numbers :  Thus  Eumf ord 
obtained  6,195;  DuLong,  6,962;  Andrews, 
6,850;  and  Favre  and  Silbermann,  7,183.6. 
These  numbers  mean  so  many  gramme- 
calories,  and  the  number  7,183.6  is  supposed 
to  be  the  most  accurate.  In  their  experi- 
ments, in  order  to  allow  for  the  loss  of  heat 
due  to  radiation,  a  preliminary  experiment 
was  made  with  the  body  whose  heat  was 
sought,  the  only  object  of  which  was  to  as- 
certain approximately  the  increase  of  tem- 


TIIERMOTAXIS  AND  METABOLISM     103 

perature  of  the  cooling  water.  If  this  in- 
crease be  10°,  for  example,  the  temperature 
of  the  water  calorimeter  was  reduced  one- 
half  this  number — that  is  to  say,  5°  below 
the  temperature  of  the  atmosphere.  By 
this  method  the  water  of  the  calorimeter 
receives  as  much  heat  from  the  atmosphere 
during  the  iirst  part  of  the  experiment  as 
it  loses  by  radiation  during  the  second 
part.  This  procedure  is  called  Kumford's 
compensation.  In  the  human  calorimeter 
the  air  tube  must  be  of  considerable  size 
for  the  air  to  enter,  and  necessarily  per- 
mits of  considerable  loss  of  heat  by  the  air 
constantly  traversing  the  instrument.  I 
have  tested  my  calorimeter  before  and 
after  the  performance  of  the  experiments. 
All  results  by  my  calorimeter  must  have 
15.5  per  cent,  added  to  them,  that  they  may 
be  accurate.  In  this  paper  I  have  made 
the  percentage  of  error  16  per  cent.,  as  the 
mean  of  several  experiments  showed  this 
to  be  the  average  error  of  the  instrument. 


104  ISAAC  OTT:  FEVER 

The  constancy  of  the  error  made  the  ap- 
paratus one  of  precision  for  scientific  work. 

In  my  experiments  upon  man  the  calcu- 
lation was  made  in  the  same  manner.  The 
specific  heat  of  the  body  was  taken  to  be 
0.83. 

In  estimating  the  moisture  I  used  Voit's 
little  respiration  apparatus,  taking  the 
moisture  of  the  air  of  the  room  and  deduct- 
ing it  from  the  moisture  of  the  air  coming 
from  the  calorimeter.  Now,  according  to 
Helmholtz,  1,000  grammes  of  water  require 
582  calories  in  evaporation  from  the  lungs 
and  skin. 

The  glass  bulbs  were  filled  partly  with 
sulphuric  acid,  and  weighed  upon  a  delicate 
balance  before  and  after  the  absorption  of 
moisture  from  the  air. 

By  placing  a  pulley  outside  the  calori- 
meter and  attaching  to  a  leather  rope  a 
fourteen  pound  weight,  the  man  within  the 
instrument  was  able  to  exercise.  The 
leather  band  entered  one  of  the  air  holes 


THERMOTAXIS  AND  METABOLISM     105 

of  the  instrument.  In  this  manner  it  was 
found :  1.  That  a  man  weighing  one  hun- 
dred and  ninety-two  pounds,  during  the 
afternoon  produced  410  heat  units  per 
hour  on  an  average  and  not  512  as  calcu- 
hited  by  oxidation  changes  and  the  amount 
of  egesta.  2.  Of  the  whole  amount  of  heat 
dissipated,  about  14  per  cent,  is  thrown  off 
by  the  hmgs.  3.  The  elevation  of  about 
five  tons  an  hour  a  foot  high  doubles  the 
hourly  heat  production. 

The  study  of  the  calorimetry  of  malarial 
fever  has  never  been  attempted,  except  by 
a  study  of  the  changes  in  the  leg  or  arm. 
Langlois  attempted  by  an  air  calorimeter 
to  study  the  heat  production  in  pneumonia 
of  children,  but  the  instrument  is  by  its 
construction  so  inaccurate,  that  it  will  give 
only  very  gross  changes. 

The  instrmnent  used  in  the  study  of  the 
malarial  paroxysm  is  accurate  in  its 
workings  as  has  been  already  detailed. 
Through  the  great  kindness  of  Dr.  J.  F. 


106  ISAAC  OTT:  FEVER 

Berg,  of  Plainfield,  N.  J.,  I  was  able  to 
study  upon  the  person  of  Mr.  W.  W. 
Schenk,  the  first  accurate  calorimetry  of 

malarial  paroxysms.    Mr.  S was  5  feet 

91/^  inches  in  height,  aged  twenty-nine,  a 
farmer,  and  the  chill  he  had  was  the  fourth 
one.  During  the  course  of  this  tertian  in- 
termittent fever,  he  was  taking  no  medi- 
cine. He  ate  a  very  light  breakfast  at 
7.30  A.  M.  At  8  A.  M.  his  temperature  was 
98,  at  9.30  a.  m.,  99.2,  felt  catching  pains 
in  the  nape  of  the  neck;  at  10.18  a.  m.,  he 
entered  the  calorimeter,  temperature  100.1. 
While  in  the  calorimeter  he  had  chills  run- 
ning up  and  down  his  back,  his  hands  felt 
cold,  and  he  had  a  general  sense  of  chilli- 
ness. Upon  leaving  the  instrument,  11.18 
A.  M.,  his  pulse  was  84,  temperature,  101.85 ; 
10.35  A.  M.,  thirsty,  feels  badly,  looks  pale, 
bones  and  head  ache,  has  a  pinched  and 
anxious  look ;  pulse  92.  At  11.47  a.  m., 
again  entered  the  calorimeter,  tempera- 
ture, 101.4,  left  instrument  at  12.48  p.  m., 


THERMOTAXIS  AND  METABOLISM     107 

temperature,  102.0;  pulse,  112;  complains 
of  heat  while  in  instrument,  face  flushed, 
hands  moist.  At  1.15  p.  m.  ate  a  fair  din- 
ner. At  1.40  p.  M.,  pulse  84;  temperature, 
100.6;  headache,  face  flushed,  some  per- 
spiration. 2  p.  M.,  temperature,  100.2, 
entered  calorimeter;  3  p.m.,  left  it,  pulse, 
84;  inside  of  calorimeter  moist  from  per- 
spiration, he  noted  the  musty  odor  for  the 
first  time  in  the  instrument.  8  p.  m.,  tem- 
perature, 98.2;  feels  quite  good;  had  four 
movements  of  bowels,  supposed  to  be  due 
to  water  not  accustomed  to. 

Second  day. — 7.30  a.  m.,  ate  a  good  break- 
fast, entered  calorimeter  at  9.53  a.  m.,  tem- 
perature 99.0;  left  instrument  at  10.53 
A.  M.,  temperature,  99%;  pulse,  84;  at  11.22 
A.  M.,  entered  calorimeter,  temperature, 
99.25.  At  12.22  p.  m.,  left  it,  temperature, 
99.25;  had  another  movement  of  bowels, 
took  a  whisky  before  dining  at  1  p.  m. 

At  1.35  p.  M.,  again  entered  the  calori- 
meter, temperature,  99.2;  left  it  at  2.35 


108  ISAAC  OTT :  FEVER 

p.  M.,   temperature,   99.7 ;   pulse,   92 ;   felt 
good,  and  left  for  home  on  Saturday. 

On  following  Sunday  had  a  light  chill. 
No  chills  since.  One  week  since  the  last 
chill  he  again  entered  the  calorimeter  for  a 
test  of  his  normal  heat  production.  He 
was  well,  and  ate  heartily.  On  the  prev- 
ious day  he  was  engaged  in  very  laborious 
work. 

By  means  of  the  electric  light  (which 
gives  a  very  uniform  heat)  of  one  candle 
power,  he  was  able  to  read  the  morning 
news  while  his  heat  production  was  being 
taken.  It  was  found  by  burning  absolute 
alcohol,  that  with  the  electric  light,  the  er- 
ror was  2.8  per  cent,  which  was  to  be  de- 
ducted from  the  amount  of  heat  production 
registered  by  the  calorimeter. 

From  a  study  of  Fig.  12  it  is  found  that 
during  the  initial  stage  or  chill-period  of 
a  malarial  paroxysm,  the  dissipation  is  not 
as  great  as  at  other  times,  and  the  heat 
production  is  enormously  increased.    After 


THERMOTAXIS  AND  METABOLISM     109 

the  fever  reached  its  height,  the  previous 
great  rise  of  heat  production  was  suc- 
ceeded by  a  great  fall,  according  to  the  law 
of  compensation.  Here  high  temperature 
is  not  an  index  of  a  correspondingly  high 
production  of  heat. 

In  the  stage  of  defervescence,  heat  dis- 
sipation is  greatly  increased  and  heat  pro- 
duction does  not  regain  its  original  height. 
It  is  only  during  the  sweating  stage  that 
the  excess  of  moisture  comes  over  in  the 
sulphuric  acid  bulbs  on  the  fever-day.  If 
the  heat  production  on  the  chill  day  and  on 
the  succeeding  day  is  compared  with  that 
of  the  normal  day,  it  will  be  found  to  be 
on  the  chill-day  79.3  heat  units  in  excess, 
and  on  the  succeeding  day  9.6  heat  units  in 
deficit.  This  is  a  much  greater  increase 
than  that  seen  in  the  septic  fever  of  ani- 
mals. 

These  observations  show  how  fever  in 
man  is  originated,  that  is,  usually  heat  pro- 
duction runs  rapidly  ahead  of  heat  dissi- 


no  ISAAC  OTT:  FEVER 

pation,  which  is  partly  lessened,  and  the 
temperature  is  elevated.  On  the  next  day 
after  the  malarial  paroxysm  there  was  a 
slight  fever,  and  the  heat  production  on  the 
average  was  lower  than  on  tlie  preceding 
day. 

There  is  every  reason  to  l)elieve  that  in 
a  continued  fever  this  increase  of  heat  pro- 
duction does  not  usually  last  many  days, 
but  that  the  fever  continues  because  of  an 
altered  relation  between  heat  production 
and  heat  dissipation,  without  regard  to  an 
increased  or  diminished  heat  production. 
These  observations  confirm  a  modified 
theor^^  of  Liebermeister's.  The  theor}^  of 
Traube,  that  fever  causes  a  vaso-motor 
spasm ;  that  of  Marey,  that  a  vaso-paraly- 
sis  exists;  or  the  more  recent  view  of 
Rosenthal,  that  of  heat  retention — all  these 
theories  contain  only  a  germ  of  truth,  that 
is,  during  the  chill  and  fever  there  is  a 
lessened  dissipation  of  heat  when  compared 
with  the  sweating  stage.     Appended  are 


THERMOTAXIS  AND  METABOLISM     111 

the  calorimetrical  results  upon  which  Fig. 
12  is  founded. 

"ciull"  day. 

A.  T.  =  Air  temperature. 
C.  T.  =  Calorimeter  temperature. 
E.  T.  ^  Temperature  of  exit  air  tube. 
M.  T.  =  Temperature  of  mouth  tube. 
Litres  3=  Amount  of  air  aspirated  through  the  calori- 
meter. 


A.M. 

A.T. 

C.  T.      E.  T. 

M.T. 

Meter 

10.18 

73.3 

67.70       20.6 

101.1 

Litres      51.37 

11.18 

72.8 

68.38       21.1 
.68 

101.85 

Weight  138  9/50 

.75 

H.D 

.=:  369.1 

H.P. 

=  569.8 

A.M. 

A.T. 

C.  T.       E.  T. 

M.  T. 

Meter 

11.47 

73.1 

68.36       21 

101.85 

Litres      50.40 

12.47 

74.0 

69.01       21.6 

+.65 

102.00 

Weight  137  29/50 

.15 

H.D 

.  =  354.0 

H.P. 

=  371.1 

P.M. 

Meter 

2 

75.3 

68.95       21.6 

100.2 

Litres      47.92 

3 

73.9 

69.57       21.8 
+  .62 

100.6 

Weight  138  40/50 

H.D 

.  =  373.1 

H.P. 

=  419.2 

112  ISAAC  OTT:  FEVER 

DAY    AFTEE    THE    CHILL. 


A.M. 

A.  T. 

C.  T.       E.  T. 

M.  T. 

Meter 

9.53 

73.7 

69.14       21.2 

99.0 

Litres      54.53 

10.53 

75.3 

69.69       22.2 
.55 

99.4 

Weight  136  40/50 

A 

H.D 

.  =  355.4 

H.P. 

=  400.8 

A.M. 

A.  T. 

C.  T.       E.  T. 

M.  T. 

Meter 

11.22 

74.3 

69.68       21.8 

99.25 

Litres      51.50 

12.22 

75.2 

70.29       22.2 
.61 

99.25 

Weight  136  31/50 

H.D 

.  =  335.8 

H.P. 

=  335.8 

P.M. 

Meter 

1.35 

77.8 

70.22       22.2 

99.2 

Litres      52.15 

2.35 

75.8 

71.75       22.4 
.53 

99.7 

Weight  137  44/50 

.5 

H.D 

.  =  338.7 

H.P, 

,  =  395.9 

NORAIAL    DAY ONE    WEEK    AFTER    HE    HAD    A    CHILL 


A.  M. 

A.T. 

C.T. 

E.  T. 

M.T. 

Meter 

11.06 

71.0 

65.60 

19.0 

98.05 

Litres      52.51 

12.06 

72.2 

66.20 
.60 

20.2 

98.85 

Weight  138.58 

.80 

H.D 

.  =  373.8 

H.P. 

=  414.0 

THERMOTAXIS  AND  METABOLISM      113 

P.M.      A.  T.       C.  T.  E.  T.       M.  T.       Meter 

12,24       72.2       66.16  20.0         98.85    Litres      50.04 

1.24       72.0       67.78  20.4         98.85    Weight  138.44 


.62  0 

H.  D.  =  342.88     As  no  electric  light,  add   167o  =  54.86 
H.D.  =  397.74 
H.  P.  =  397.74         No  moisture  came  over. 

P.M. 

2.35       73.4       66.86       20.6         98.5       Litres      48.73 
3.35       74.1       67.34       21.0         99.4       Weight  140.12' 


.48 


H.  D.  =  264.82     No  electric  light,  add  16%  ■=  42.37 
H.D.  =  307.19 
H.  P.  =  411.19         No  moisture  came  over. 

Through  the  great  kindness  of  Dr.  F.  G. 
Benedict  of  the  Carnegie  Nutrition  Labora- 
tory, I  have  obtained  a  translation  of  a 
paper  ^^  upon  the  heat  phenomena  in  ma- 
larial fever,  which  confirms  my  researches 

21  A.  A.  Lichacheff  and  P.  P.  Avroroff.  "Investiga- 
tions of  Gaseous  and  Heat  exchange  in  Fevers.  (Febris 
intermittens  tertian.)"  A  separate  reprint  from  volume 
V,  parts  3  and  4.  Reports  of  the  Imperial  Military 
Medical  Academy.  St.  Petersburg.  Printing  office  of 
M.  Merusbera,  Nevski  prospect  8,  1902. 


114  ISAAC  OTT:  FEVER 

made  ten  years  previous  to  theirs.  As  it 
is  rather  inaccessible  to  many  of  ns  I  shall 
give  you  an  abstract  of  considerable  extent. 


LECTURE  III 


LECTUEE  III 

Gentlemen. — In  this  lecture  I  shall  con- 
tinue the  study  of  malarial  fever  and  the 
metabolism. 

Their  investigations  were  made  with  a 
water  calorimeter  of  Professor  Paschutin, 
and  at  the  same  time  they  measured  the 
gaseous  exchanges.  (The  calorimeter  is 
described  by  Lichacheff.  Heat  production 
in  a  healthy  i^erson  when  in  relative  rest. 
Dissertation,  St.  Petersburg,  1893.  A 
description  of  calorimeter  of  Paschutin.) 

The  calorimeter  was  oval  in  form,  about 
3  yards  in  length  and  the  same  in  height, 
with  a  capacity  for  air  of  about  2.7  cubic 
meters.  In  this  space  is  a  metallic  net  in- 
stead of  a  floor,  with  a  bed  consisting  of 
a  rubber  mattress  and  pillow  inflated  with 

air.     For  sitting  a  bench  is  placed  in  the 

117 


118  ISAAC  OTT:  FEVER 

chamber  and  the  person  can  make  two  to 
three  steps.  The  chamber  can  be  closed 
hermetically  by  two  covers  (one  inside  the 
other,  in  which  are  two  glass  windows). 
The  ventilation  is  by  a  special  suction  air- 
pump,  which  is  operated  by  a  gas  motor, 
and  can  suck  out  150  liters  of  air  in  a  min- 
ute. The  ventilation  was  ordinarily  80 
liters  in  a  minute,  or  about  5  cubic  meters 
of  air  an  hour.  The  air  entering  the  cham- 
ber was  first  deprived  of  C02  and  water  by 
absorption  by  potash  and  concentrated  sul- 
phuric acid.  The  air  coming  out  of  the 
chamber  was  conveyed  through  sulphuric 
acid  and  potash.  There  was  an  electric 
light  in  the  chamber,  of  one  candle  power, 
and  its  heat  estimated.  The  temperature 
of  the  apparatus  ranged  from  17-20  C. 

For  signaling  purposes  there  was  a  bell 
and  for  talking  a  speaking  tube  wliich  was 
divided  by  a  thin  impenetrable  gauze  or 
cover  of  natural  rubber. 

Before  beginning  the  experiment,  they 


THERMOTAXIS  AND  METABOLISM     119 

weighed  the  food,  the  jars  of  urine,  feces, 
the  linen  wear,  the  clothes  and  bed  of  the 
sick  one.  The  moisture  of  air  in  the  ap- 
paratus was  determined  with  the  aid  of  a 
psychrometer.  The  patient  was  weighed 
and  immediately  placed  in  the  apparatus. 
After  closing  the  covers  of  the  calorimeter, 
which  required  about  half  an  hour,  the 
ventilating  air  would  be  admitted  into  the 
chamber  and  the  stirring  of  the  water  in 
the  calorimeter  was  commenced  for  the 
purpose  of  reading  an  even  temperature  in 
the  apparatus.  However,  the  calorimeter 
determination  would  begin,  not  at  once,  but 
an  hour  or  more  later,  with  the  object  that 
during  that  time  it  would  settle  itself  to 
the  well-known  more  or  less  constant  rela- 
tionship between  the  temperature  of  the 
apparatus  and  the  temperature  of  the  sur- 
rounding moist  conditions,  which  are  to  be 
observed  in  reaching  a  high  degree  of  pre- 
cision in  the  indications  of  the  apparatus. 
In  order  to  obtain  the  results  as  to  the  in- 


120  ISAAC  OTT:  FEVER 

tensity  of  heat  production  and  exchange 
of  matter  during  different  moments  of  the 
fever  attack,  the  test  of  the  whole  24  hours 
was  broken  up  into  separate  periods,  each 
continuing  2  hours,  thus  we  had  11  periods 
of  2  hours  each.  At  the  end  of  each  period 
she  would  have  a  change  of  temperature 
during  y^  hour,  and  we  would  record  the 
readings  of  all  the  thermometers  of  tlie 
apparatus  (calorimeter,  as  well  as  under 
the  skin,  and  that  of  the  room).  For  a 
still  more  accurate  observation  we  re- 
corded the  thermometers  not  only  at  the 
end  of  two  hour  periods,  but  also  in  the 
middle  of  it,  that  is,  we  would  make  records 
each  hour,  also  the  temperature  of  the  pa- 
tient (a  woman  during  the  fever  attack) 
was  measured  each  liour. 

The  patient,  Anastasia  Zarerski,  was  17 
years  old,  weighing  49.321  kilograms.  The 
fever  was  a  tertian  intermittent.  They 
made  observations  during  the  attack  of 
fever  on  May  12  and  May  14,  and  a  third 


TIIERMOTAXIS  AND  METABOLISM     121 

series  of  observations  during  the  time  of 
absence  of  fever  on  May  18-19,  that  is,  4 
days  after  the  last  fever  attack.  After 
May  15  and  16,  she  received  quinine.  Her 
maximum  temperature  was,  at  6  p.  m., 
36.7°  C,  and  minimum,  at  11  p.  m.,  36°  C. 
During  the  rest  of  the  night  and  day  the 
temperature  kept  within  the  limits  of 
36.2°-36.6°. 

HEAT    PRODUCTION 

Heat  production  in  the  evening  hours  at 
the  beginning  of  the  observation  stood  at 
about  85  kilo-calories  per  hour,  then  it  be- 
gan to  fall  quite  rapidly  and  by  5-7  in  the 
morning  it  reached  its  minimum,  whicli  was 
about  Y2  the  quantity  of  the  evening  fig- 
ures— 46  calories  per  hour.  This  con- 
siderable reduction  of  lieat  production 
within  the  organism  coincided  with  the 
time  of  sleep  of  Miss  Zarerski.  During 
morning  hours  heat  production  would 
somewhat  increase  and  stood  at  a  height 


122  ISAAC  OTT:  FEVER 

of  70-65  calories  per  hour,  and  in  the  after- 
noon, from  3  to  5  p.  m.,  it  increased  still 
more,  up  to  77  calories.  Just  as  in  the 
evening  hours  we  observed  a  maximum  of 
heat  production,  so  we  also  had  a  maxi- 
mum temperature  in  normal  healthy  men. 
She  normally  had  32  calories  per  kilo  of 
weight. 

HEAT   LOSS 

The  absolute  amount  of  heat  loss  was 
maximum  91  calories  per  hour  from  7  to 
9  in  evening,  minimum,  53  calories,  from 
5  to  7  in  the  morning.  During  the  day- 
time heat  loss  was  60-70  calories  per 
hour. 

The  heat  lost  by  radiation  and  conduc- 
tion was  determined  by  noting  the  changes 
in  the  temperature  of  the  calorimeter  and 
the  changes  in  the  temperature  of  the  air 
that  passed  through  it.  Tlie  heat  lost  by 
evaporation  of  water  was  measured  by  de- 
termining the  quantity  of  water  given  off 


7P.M.       9         11      1A.M.       3  5       7  9  11      1P.M.       3 


Sit 

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Normal  day   (Lehacheff  and  Avroroff  from  Ringer). 


123 


124  ISAAC  OTT:  FEVER 

by  the  patient  through  her  skin  and  lungs, 
and  multiplying  the  same  by  0.59  calories. 
The  total  heat  production  was  obtained 
from  the  sum  of  the  values  of  heat  lost  by 
evaporation  of  water  and  by  radiation  and 
conduction,  plus  or  minus  the  retention 
or  loss  of  heat  because  of  changes  in  the 
body  temperature.  This  last  one  was  de- 
termined from  the  formula :  W  X  ( T  ± 
t)  X  S.  W  equals  body  weight,  T  equals 
temperature  of  the  body,  t  equals  value  of 
change  of  temperature,  and  S  equals  spe- 
cific heat  of  body,  which  equals  0.83.  The 
patient  was  in  the  calorimeter  for  3  days 
— one  normal  and  two  fever  days.  The 
results  are  seen  in  Figs.  13  and  14. 

HEAT    LOSS    BY    EADIATION    AND    EVAPOEATION 

Of  the  total  sum  of  heat  losses,  the  share 
of  heat  loss  by  radiation  and  heat  conduc- 
tion is  1.104  calories,  or  74.6%,  and  tlie 
share  of  heat  loss  by  evaporation  is  376 
calories,  or  25.4%. 


THERMOTAXIS  AND  METABOLISM     125 

GASEOUS    EXCHANGE 

The  elimination  of  Coo  followed  approx- 
imately the  same  order  as  did  the  develop- 
ment and  loss  of  heat  within  the  organism, 
namely,  during  evening  hours,  7  to  11,  the 
elimination  of  Coo  stood  at  the  maximum 
height,  26.5  grams  per  hour,  then  during 
the  night  (early  morning)  hours  it  fell  to 
18  grams  and  during  the  day  hours  an 
average  of  about  25  grams  per  hour.  The 
night  minimum  of  elimination  of  C02  was 
reached  earlier  than  heat  production  and 
heat  loss  of  the  organism,  so  that  at  this 
time  when  the  development  of  heat  within 
the  organism  still  continued  to  lower,  the 
elimination  of  Coo  already  started  on  its 
rise. 

WATERY    VAPOR 

Watery  vapor,  maximum  33  grams  per 
hour  in  the  night,  it  gradually  came  down 
to  its  minimum,  24.5  grams,  and  then  dur- 
ing the  morning  hours  would  rise  up  to  its 


126  ISAAC  OTT:  FEVER 

former  height.  The  amount  of  absorbed 
oxygen  during  22  hours  was  equal  to  406 
grams,  and  the  respiratory  quotient  was 
0.92. 

The  amount  of  N  eliminated  in  the  urine 
during  24  hours  was  equal  to  11.4  grams. 
During  fever  days,  Miss  Zarerski  ate  but 
little  (incomplete  hunger)  and  she  lost 
weight. 

FEVER  OBSERVATIONS 

The  stage  of  increase  of  fever  was  five 
hours  and  the  period  of  decrease  of  fever 
about  ^ve  hours.  The  chill  commenced  at 
2  A.  M.  The  temperature  normally  was 
36.1°,  and  then  rose  to  37.9°  and  then  to 
39.3°,  and  at  7  p.  m.,  was  39.7°,  when  the 
chill  stopped.  Then  the  temperature  fell 
to  normal  by  11  o'clock,  and  from  11  to  12 
the  fever  was  over.  The  duration  of  the 
whole  attack  was  about  10  hours.  The  pe- 
riod of  the  chill  was  about  3  hours. 

Heat  Production.     During  the  period  of 


THERMOTAXIS  AND  METABOLISM      127 

12-2  A.  M.,  when  there  was  no  fever,  and 
the  patient  in  complete  rest,  there  were  54 
calories  per  hour.  From  2-4  a.  m.,  when 
patient  was  also  asleep  and  woke  up  Y^  of 
an  hour  earlier  than  before,  for  she  was 
disturbed  out  of  her  sleep  for  the  purpose 
of  taking'  the  temperature,  the  heat  pro- 
duction rose  to  93  calories  per  hour,  which 
coincided  with  the  chill  and  rise  of  tem- 
perature, or  the  first  stage  of  the  fever. 
From  4-5  a.  m.,  heat  production  rose  to  the 
maximum  112  calories,  and  the  tempera- 
ture rose  to  39°,  and  the  chill  continued. 
During  the  succeeding  2  hours,  from  5-7, 
heat  production  fell  to  75-80  calories. 
After  7,  the  temperature  began  to  fall  and 
heat  production  at  the  same  time  fell  to  56 
calories ;  when  sweat  appeared,  8  to  10 
A.  M.,  the  heat  production  gave  a  second 
wave,  reaching  88  calories  per  hour,  and 
then  came  down  to  its  original  level. 

We  see  that  heat  production  of  our  first 
observation  in  fever  stands,  until  the  be- 


128  ISAAC  OTT:  FEVER 

ginning  of  the  attack  and  a  few  hours  after 
the  end  of  the  attack,  is  lower  than  normal, 
owing  to  the  diet.  During  the  fever  attack 
and  immediately  after  the  curve  of  heat 
production  stands  all  the  time  higher  than 
normal. 

Heat  production  of  the  patient  during 
the  whole  fever  attack  was  considerably 
higher  and  the  increase  comes,  almost  with- 
out exception,  from  the  period  of  rise  of 
temperature. 

General  Heat  Loss.  From  12  to  2  a.  m., 
when  the  patient  slept,  it  stood  at  65  cal- 
ories per  hour.  During  the  following  2 
hours,  when  the  chill  began,  with  a  rise  of 
temperature  the  heat  loss  was  somewhat 
decreased,  but  not  much,  coming  down  to 
56  calories.  From  4-7  heat  loss  stood  at 
its  original  level,  although  the  tempera- 
ture during  that  time  reached  39.7°.  After 
this  temperature  had  reached  its  maxi- 
mum, the  heat  loss  began  to  rise  quite 
rapidly,  and  by  8  reached  77,  and  by  9 


12P.M.  2A.M.     4  6  8  10        12      2P.M.      4 


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Fig.  14. 
Day  of  liigb  fever    (LehachefF  and  Avroroff  from 

Ringer). 
129 


130  ISAAC  OTT:  FEVER 

A.  M.,  was  up  to  112  calories,  double  the 
original  height.  From  9  to  10,  heat  loss 
stood  at  the  same  height  and  by  2  o'clock 
it  fell  to  71  calories.  From  2  to  6  p.  m.,  it 
rose  to  84  calories  per  hour,  and  after  8 
p.  M.,  when  the  patient  was  asleep,  it  came 
down  to  60  calories,  at  about  which  level  it 
stood  at  the  very  beginning  of  the  observa- 
tion. 

Comparing  the  curve  of  heat  loss  with 
normal  curve  of  heat  loss,  we  see  at  the  be- 
ginning of  the  fever  attack,  from  12-2  a.  m., 
that  heat  loss  stood  at  quite  the  same  level 
as  normal,  and  that  during  the  first  half 
of  the  attack,  that  is,  during  the  rise  of 
temperature  of  patient,  the  heat  loss  was 
somewhat  higher  than  normal,  since  the 
curve  of  the  normal  day  during  these  night 
hours  coinciding  with  the  time  of  sleep  no- 
ticeably fell.  During  the  second  half  of 
the  attack,  during  the  fall  of  temperature, 
the  heat  production  rose  much  above  nor- 


THERMOTAXIS  AND  METABOLISM      131 

mal,  exceeding  it  almost  one  and  a  half 
times. 

If  we  compare  the  curve  of  heat  loss 
with  the  curve  of  heat  production  for  the 
same  fever  day,  we  find  both  curves  in  their 
appearance  are  quite  alike  to  each  other; 
both  during  the  fever  have  a  quite  sharp, 
but  not  lasting  ascent,  then  a  rapid  fall  and 
during  the  evening  hours  they  rise  again. 
But  the  differences  in  the  curves  are  as 
follows :  the  curve  of  heat  production  dur- 
ing the  fever  attack  gives  but  one  wave, 
whilst  heat  dissipation  curve  gives  at  least 
two,  from  which  the  second  wave,  the  one 
much  lower  in  height,  comes  during  the 
second  half  of  the  attack.  The  wave  in  the 
heat  production  curve,  in  time  of  appear- 
ance, precedes  the  same  wave  in  the  curve 
of  heat  dissipation  by  about  5  hours.  The 
increase  of  heat  production  occurs  at  the 
very  beginning  of  the  attack,  at  the  time  of 
rapid  rise  of  temperature,  but  the  increase 


132  ISAAC  OTT:  FEVER 

of  heat  dissipation  is  observed  only  in  the 
second  half  of  the  attack,  during  the  fall 
of  fever  temperature  and  the  fall  of  heat 
production  which  by  that  time  succeeds  in 
coming  down  to  normal  and  gives  a  second 
rise  coinciding  in  time  with  the  appearance 
of  the  principal  wave  of  heat  loss. 

In  the  increment  of  temperature  the  de- 
crease of  heat  dissipation  either  played  no 
part  at  all  or  played  a  very  insignificant 
part.  Here  the  rise  of  temperature  in  the 
patient  was  owing  to  the  increased  develop- 
ment of  heat  in  the  body,  and  the  decrease 
of  it  was  conditional  upon  an  increased 
heat  dissipation  during  the  second  half  of 
the  attack. 

Heat  Loss  by  Evaporation  of  Water 
from  Skin  and  Lungs.  It  was  higher  than 
normal  during  the  whole  24  hours.  Dur- 
ing the  night  and  morning  the  heat  loss  by 
evaporation  was  20  calories  per  hour,  and 
in  the  afternoon  about  24  calories.  From 
8  to  10  A.  M.,  it  rose  from  20  to  29  per 


THERMOTAXIS  AND  METABOLISM      133 

hour,  and  after  10  hours  it  fell  to  22  cal- 
ories. The  maximum  of  heat  loss  coin- 
cided with  the  appearance  of  sweat.  The 
minimum  heat  loss  by  evaporation  from 
skin  and  lungs  was  19-20  calories  per  hour, 
coincided  and  took  place  from  2-6  a.  m., 
that  is,  just  during  the  period  of  chill. 

Gaseous  Exchange.  Before  the  fever 
attack,  during  sleep,  the  elimination  of  Coo 
stood  at  a  very  low  quantity,  20  grams  per 
hour.  Then  with  the  rise  of  temperature 
and  heat  production,  the  elimination  of  Coo 
began  to  rise  noticeably  and  gradually 
rose  to  34  grams,  which  coincides  in  time 
with  the  highest  point  of  temperature  from 
6  to  8  A.  M.,  though  heat  production  fell  by 
this  time  considerably.  With  the  fall  of 
temperature  during  the  second  half  of  the 
attack,  the  elimination  of  Coo  rapidly  di- 
minished too,  and  only  in  the  afternoon 
showed,  like  the  heat  production,  a  tem- 
porary increase.  There  was  a  parallel  in 
the  curves  between  heat  production  and 


134  ISAAC  OTT:  FEVER 

the  elimination  of  C02 ;  a  similar  state  was 
also  seen  normally.  There  was  no  corre- 
spondence between  the  curve  of  elimina- 
tion of  C02  and  that  of  heat  dissipation. 

Absorbed  Oxygen.  The  amount  of  oxy- 
gen absorbed  for  22  hours  was  equal  to 
563  grams  and  the  respiratory  quotient 
was  0.75.  The  absorption  of  oxygen  in 
fever  was  higher  compared  with  the  nor- 
mal in  an  average  for  22  hours. 

Nitrogen.  The  amount  of  N  eliminated 
with  the  urine  during  the  24  hours  was  10.2 
grams  less  than  normal. 

Their  general  deductions  (after  the  sec- 
ond experiment  with  the  same  patient), 
were  as  follows: 

Max.  For  22  hours 

Temp.  H.P.  Coo     H02      O2      R.A. 

Normal     ..36.0 — 36.6(C)    1.48    calories.      513      637     406      0.92 

Mild  fever 
2nd  ob- 
servation 37.9  1.492        "  520      638      474      0.80 

Severe 
fever  1st 
observa- 
tion    ...35.8 — 39.7  1.633        "  587      852      563      0.76 

In  both  observations,  during  the  whole 
fever  period  there  was  observed  a  distinct 


THERMOTAXIS  AND  METABOLISM     135 

increase  of  both  heat  production  and  heat 
loss,  and  the  increase  of  heat  production 
occurred  ahnost  without  exception  during 
the  rise  of  temperature  and  an  increase  of 
heat  dissipation  occurred  during  the  pe- 
riod of  decline  of  temperature. 

In  both  of  their  fever  observations  there 
was  a  distinct  rise  of  gaseous  exchange; 
the  increase  of  elimination  of  C02  was 
mainly  during  the  period  of  rise  of  tem- 
perature and  the  elimination  of  water  was 
sharply  raised  during  the  period  of  fall  of 
temperature. 

They  also  made  experiments  upon  them- 
selves while  working  under  normal  condi- 
tions. The  mechanical  labor  consisted  in 
lifting  a  weight  of  one  pound  (about  36 
lbs.)  standing  upon  a  stool  at  a  height  of 
60  centimeters,  and  letting  it  down  to  the 
floor  for  2  hours  after  a  previous  rest  of 
2  hours,  then  a  rest  of  4  hours. 

They  found  that  under  physiological 
conditions  the  organism  can  considerably 


136  ISAAC  OTT:  FEVER 

increase  within  itself  the  production  of 
heat  without  causing  thereby  any  sub- 
stantial rise  of  its  own  temperature. 
Hence,  they  infer  that  the  fever  rise  of 
temperature  in  a  strictly  physical  sense 
depends  chiefly  upon  the  rise  of  heat  pro- 
duction. From  a  physiological  point  of 
view  we  see  in  this  fact  that  a  very  sub- 
stantial part  is  undoubtedly  played  by  the 
thermo-regulating  facilities  of  the  organ- 
ism. 

METABOLISM   IN    FEVER 

Hirsch  and  Miiller  have  shown  that  as 
the  liver  has  the  highest  temperature,  the 
greater  metabolic  changes  must  be  found 
in  this  organ.  The  question  then  arose, 
whether  after  puncture  of  the  thermogenic 
centers  in  animals  freed  of  glycogen  there 
ensued  an  elevation  of  temperature.  Roily 
found  that  in  twenty-one  rabbits  with  no 
glycogen  in  the  muscles  or  liver,  puncture 
of  the  thermogenic  center  did  not  cause  an 


THERMOTAXIS  AND  METABOLISM     137 

elevation  of  temperature.  In  two  rabbits 
only  was  there  a  rise  of  0.4  and  of  0.2 "^ 
Fahrenheit.  To  animals  free  of  glycogen 
he  fed  simple  sirup  to  produce  glycogen 
again ;  puncture  of  the  brain  then  produced 
fever.  In  glycogen-free  animals  the  injec- 
tion of  bacteria  (pneumococcus  and  bac- 
terium coli)  produced  a  fever;  hence  in 
glycogen-free  animals  infection  generates 
fever,  but  in  the  same  animal  thermogenic 
puncture  does  not. 

Roily  also  found  that  albumoses  and  pep- 
tones do  not  generate  fever  in  glycogen- 
free  animals.  Ott  ^  proved  that  they  gen- 
erated fever  in  animals  in  normal  condi- 
tion. 

Roily  also  found  that  there  was  no  in- 
crease (or  only  a  small  one)  of  urinary 
nitrogen  after  thermogenic  puncture  in  gly- 
cogen-free animals.  Hence  Roily  supports 
Krehl  and  Schultz  in  their  theory  that  the 
small  increase  of  urinary  nitrogen  after 

1  Jour,  of  Physiol,  1887,  VIII,  218. 


138  ISAAC  OTT:  FEVER 

brain  puncture  is  due  to  the  hyperthermia 
and  is  not  a  direct  result  of  the  puncture 
of  the  thermogenic  center.  In  the  glyco- 
gen-free  animals  not  only  does  the  thermo- 
genic puncture  produce  no  fever,  but  the 
increase  of  urinary  nitrogen  does  not  take 
place  to  any  extent.  Roily  believes  that 
in  neurogenic  fever  the  increase  of  urinary 
nitrogen  is  due  to  the  hyperthermia  and 
not  to  the  irritation  of  the  thermogenic 
nerves.  The  greater  increase  of  urinary 
nitrogen  in  fever  generated  by  bacteria  is 
due  to  an  increased  destruction  of  protein 
produced  by  the  infection  itself.  In  infec- 
tious fever  there  is  from  the  beginning  an 
abnormal  destruction  of  proteid. 

Hirsch,  Muller  and  Roily  hold  to  the 
theory  that  in  fever  we  have  two  parallel 
processes:  (1)  a  specific  breaking  up  of 
the  proteid  by  the  bacteria,  and  (2)  a  cen- 
tral excitation  in  the  sense  of  a  neurogenic 
fever. 


THERIMOTAXIkS  and  metabolism      139 

Aronsohn  has  opposed  this  view.  He 
believes  that  the  increased  destruction  of 
proteid  is  dependent  upon  the  nerves  and 
ferments.  The  theory  of  a  toxic  destruc- 
tion of  proteid  is  without  foundation.  An 
increased  destruction  of  proteid  ensues  ac- 
cording to  him  (1)  where  there  is  a  paucity 
of  glycogen  and  fats;  (2)  in  toxic  fever 
and  in  excessive  irritation  of  the  nerves, 
and  (3)  in  cachexias.  The  increased  de- 
struction of  proteid,  according  to  Aron- 
sohn, is  a  result  of  the  fever-process  due  to 
heightened  innervation  of  the  cells — an  ir- 
ritation of  a  thermogenic  center. 

Senator  and  Eichter  (1)  found  results 
differing  from  those  of  Hirsch,  Mtiller  and 
Eolly.  ,  They  also,  by  means  of  strychnia, 
made  animals  free  of  glycogen,  and  then 
made  a  puncture  into  a  heat  center,  corpus 
striatum,  which  was  followed  by  a  tempera- 
ture nearly  as  high  as  in  animals  with  gly- 
cogen.    They  inferred  that  glycogen  was 


140  ISAAC  OTT:  FEVER 

not  necessary  to  the  generation  of  fever 
and  no  special  substance  was  needed  to  pro- 
duce hyperthermia. 

Ott  and  Scott  ^  have  studied  the  effect 
of  an  agent,  tetra-hydro-beta-naphthyla- 
mine,  upon  glycogen-free  animals.  This 
body  is  a  pure  nervous  agent  in  the  pro- 
duction of  fever.  One  of  us  has  in  another 
place "  shown  that  it  acts  only  when  the 
corpus  striatum  and  tuber  cinereum  are 
present.  If  only  the  corpora  striata  are 
removed,  still  the  irritations  of  the  thermo- 
genic centers  in  the  tuber  by  it  are  sufficient 
to  produce  a  fever. 

We  did  not  find  it  an  easy  matter  to  free 
the  animal  completely  of  glycogen,  but  we 
had  some  with  complete  absence  of  glyco- 
gen either  in  the  liver  or  muscles. 

We  showed  that  tetra-hydro-beta-naph- 
thylamine  will  produce  fever  in  a  glycogen- 

2  Ott  and  Scott.     Journal  of  Experimental  Medicine, 
Vol.  IX,  No.  6,  1907. 

3  Ott.     Medical  Bulletin.     1898.     XX.     411. 


THERMOTAXIS  AND  METABOLISM      141 

free  animal.  The  fever  here  must  be  due 
to  a  using  up  of  the  protein.  The  metab- 
olism of  the  protein  is  set  into  activity 
by  the  stimulation  of  the  thermogenic  cen- 
ters in  the  corpus  striatum  and  the  tuber 
cinereum,  for  the  removal  of  these  cen- 
ters prevents  the  naphthylamine  from 
causing  a  rise  of  temperature. 

Naphthylamine  is  a  powerful  thermo- 
genic stimulant  like  the  poisons  of  infec- 
tious fevers.  Here  the  naphthylamine 
stimulates  the  nerve  centers  to  act  upon 
the  protein,  initiating  changes  in  it.  These 
facts  do  not  support  the  views  of  Krehl 
and  Eolly  that  puncture  of  the  brain  acts 
only  on  glycogen,  while  the  infectious 
fevers  produce  a  toxic  metabolism  of  pro- 
tein. 

Nearly  all  observers  agree  that  in  fever 
there  is  an  increased  protein  metabolism, 
but  no  increased  fat  metabolism  except 
such  as  may  result  from  inanition  in  the 
individual.     There  is  every  reason  to  be- 


142  ISAAC  OTT:  FEVER 

lieve  that  in  both  puncture  of  the  thermo- 
genic centers  and  in  the  infectious  fevers, 
fever  is  produced  by  an  action  on  the  ther- 
mogenic centers. 

BIBLIOGRAPHY 

Aronsohn. — Allgemeine  Fieberlehre,  1906  ;  Zeit. 

f.  klin.  Med.,  1907,  LXXVIII,  153. 
Lusk.— "The  Science  of  Nutrition,"  1906. 
Roily.— Deut.     Archiv     f.     klin.     Med.,     1903, 

LXXVIII,  250. 

PROTEIN    METABOLISM 

Dr.  Lusk,  from  250  experiments  upon 
dogs,  in  speaking  of  the  specific  dynamic 
action  of  food  stuffs,  found  that  the 
cause  of  it  lay  not  in  the  absorptive  or  ex- 
cretive mechanisms  but  in  the  interplay  be- 
tween the  living  cells  and  the  nutrient  ma- 
terial, the  sugars  and  amino-acids  in  the 
blood.  There  was  a  marked  increase  in 
heat  production  after  the  ingestion  of 
sugar,  but  in  the  4  to  5  hours  the  heat  pro- 
duction regained  the  level  of  basal  metab- 


THEEMOTAXIS  AND  METABOLISM      143 

olism.  He  believes  the  cause  of  this  in- 
creased heat  production  to  be  due  to  the 
mass  action  of  the  sugar  molecules  reacting 
upon  the  liver  cells.  When  alcohol  was 
added  to  the  glucose  the  heat  production 
was  raised  above  the  level  to  which  glucose 
alone  would  have  raised  it,  and  the  alco- 
hol was  oxidized  in  preference  to  the  carbo- 
hydrates. Lusk  also  studied  three  amino- 
acids  convertible  into  sugar  and  urea  and 
found  that  they  could  be  given  without 
appreciable  increase  of  heat  production. 
The  result  that  followed  the  administration 
of  amino-acids  was  like  that  which  occurred 
after  meat  ingestion,  in  that  the  amount 
of  increase  of  heat  production  was  pro- 
portional to  the  quantity  metabolized.  He 
holds  the  view  that  the  great  increase  in 
heat  production  is  due  to  stimulation  of 
the  protoplasm  to  higher  activity  through 
the  mass  action  of  accumulated  amino- 
acids.  He  also  believes  that  the  highest 
heat    production    is    coincident    with    the 


144  ISAAC  OTT:  FEVER 

highest  metabolism  of  amino-acids,  and 
that  the  amino-acids  themselves  do  not  lie 
in  the  tissues  to  act  as  stimuli  without  be- 
ing involved  in  highly  active  metabolism. 
It  was  shown  that  specific  intermediary 
acids  were  formed  in  metabolism.  These 
were  the  real  stimuli,  and  when  ingested 
protein  was  reconstructed  into  body  pro- 
tein the  amino-acids  involved  in  this  re- 
action did  not  cause  an  increase  in  heat 
production.  It  might  be  stated  that  living 
cells  metabolized  carbo-hydrates  and  fats 
in  increased  quantity  when  these  were 
present  in  large  amounts  in  the  surround- 
ing fluid,  and  that  they  were  also  stimulated 
to  a  higher  heat  production  during  metab- 
olism of  certain  amino-acids  to  an  extent 
entirely  out  of  proportion  to  their  energy 
value.^ 

High  temperature  by  itself  increases  the 
metabolism  of  proteins.  Pflueger  has  es- 
timated that  for  every  increase  of  1  degree 

^  Med.  Record.     1914.     June  27.     P.  1189. 


THERMOTAXIS  AND  METABOLISM     145 

C  ill  a  rabbit's  temperature,  the  heat  pro- 
duction increases  about  6  per  cent.,  and  the 
same  has  been  found  to  be  true  for  man 
when  subjected  to  artificial  heat.  But  this 
is  only  one  cause  of  the  increased  produc- 
tion of  heat  in  hyperthermia. 

The  infectious  fevers  have  an  increased 
nitrogenous  metabolism.  In  an  animal  in 
starvation  an  equilibrium  of  metabolism 
is  easily  obtained.  The  nitrogen  in  the 
urine  readily  gives  the  amount  of  protein 
consumed,  and  albumen  administered  by 
the  mouth  easily  keeps  up  a  nitrogen  bal- 
ance. 

In  May's  experiments  upon  rabbits  the 
nitrogen  after  intravenous  injection  of  a 
broth  of  bacillus  of  swine  erysipelas,  the 
temperature  was  39.5  and  nitrogen  output 
1.79;  on  the  fourth  day  the  temperature 
was  41.2°  C.  and  nitrogen  output  1.81;  and 
on  the  fifth  day  it  was  41.2  to  40.7,  nitrogen 
output  2.45  grams. 

In  Staehlin's  experiments  dogs  were  in- 


146  ISAAC  OTT:  FEVER 

oculatecl  subcutaneously  with  the  trypan- 
osome  of  Surra.  The  animal  was  in  a  con- 
dition of  nitrogen  equilibrium ;  it  was  kept 
in  the  Pettenkofer  respiration  apparatus 
and  the  output  of  nitrogen,  carbon  and 
water  determined.  He  also  made  calori- 
metrical  valuations  of  the  food,  urine  and 
feces.     Muscular  work  was  avoided. 

During  the  1st  fever  day  the  dog  took 
all  his  food,  yet  the  outgo  of  nitrogen  ex- 
ceeded the  in-go  by  a  considerable  amount. 
From  the  4th  to  7th  day  of  the  fever,  the 
output  of  nitrogen  was  44%  above  the  ni- 
trogen of  the  ingesta.  From  the  7th  day  to 
the  10th  day,  the  output  of  nitrogen  was 
higher  than  in  the  normal  period,  although 
the  amount  of  food  was  diminished,  and 
from  the  10th  to  12th  days — the  terminal 
days — the  nitrogen  deficit  was  on  the  10th 
day  7.1  grams,  and  then  diminished  to  one- 
half  this  amount.  According  to  these 
figures  the  animal  lost  about  20%  the  orig- 
inal nitrogen  present  in  the  body. 


TIIERMOTAXIS  AND  METABOLISM     147 

Sharpe  and  Simon  ^  found  in  a  case  of 
malaria  that  there  was  a  tendency  for  the 
rise  of  temperature  to  be  accompanied  by 
an  increased  output  of  total  nitrogen  and 
less  uniformly  of  creatinine.  In  two  dogs, 
in  whom  the  fever  was  preceded  by  rigor, 
the  output  of  uric  acid  was  increased. 

Shaffer  *'  has  shown  that  the  giving  of 
large  amounts  of  carbo-hydrates  on  a  low 
protein  diet  may  completely,  or  almost 
complet(;ly,  maintain  the  patient  in  nitro- 
gen balance  throughout  the  disease. 

There  is  no  parallelism  between  the 
amount  of  nitrogen  in  the  urine  and  the 
temperature  of  the  body.  Pribram  and 
Eobitschek  and  subsequently  Furbringer 
and  Zuelzer  found  that  the  elimination  of 
sulphur  to  a  certain  extent  ran  parallel 
with  the  variable  urinary  nitrogen. 

Salkowsky   further  found   that   the   in- 

5  Sharpe  and  Simon.  Journal  of  Experimental  Medi- 
cine, Vol.  XX.     No.  3,  p.  282. 

«  Shaffer.  Journal  Am.  Med.  Association,  1908,  Vol. 
51,  p.  974. 


148  ISAAC  OTT:  FEVER 

creased  outgo  of  nitrogen  was  accompanied 
also  by  an  increased  elimination  of  potash 
salts. 

Leatlies  also  found  in  hospital  patients 
that  the  creatinine  was  increased  in  fever. 
Linsen  and  Schmid  found  the  purin  bodies, 
ammonia  and  amino-acids,  increased. 

Graham  and  Poulton  "^  by  means  of 
a  chamber  of  heated  steam  elevated  their 
temperature  to  104°  F.,  but  notwithstand- 
ing the  temperature  there  was  no  increase 
of  metabolism  by  the  high  temperature. 

Shaffer  and  Coleman  ^  found  that  in  ty- 
phoid fever,  with  an  abundant  diet  of  fat 
and  carbohydrates,  there  was  a  nitrogenous 
equilibrium  with  a  low  intake  of  protein. 

Kocher  ^  has  shown  that  a  very  liberal 
diet  of  as  much  as  80  calories  per  kilogram 
did  not  retard  the  protein  metabolism  of 

7  Graham  and  Poulton.     Quarterly  Journal  Med.,  Oct., 
1912,  p.  8. 

8  Shaffer   and   Coleman.     Archiv.   Int.    Med.     10Q8,   p. 
538. 

oKoclier.     Archiv  f.   Klin.    Med.     1914.     CXV.     82. 


THERMOTAXIS  AND  METABOLISM     149 

typhoid  fever  in  the  early  period  of  ty- 
phoid, as  they  did  later.  He  holds  that  the 
protein  destruction  is  due  to  the  action  of 
a  special  toxic  substance  upon  protoplasm. 

Coleman  ^^  has  also  found  that  food  does 
not  increase  the  heat  production  or  tem- 
perature in  typhoid  fever,  even  when  given 
in  large  amounts,  at  least  where  the  quan- 
tity of  protein  is  kept  relatively  low.  A 
liberal  diet  in  fever  will  not  raise  the  tem- 
perature. He  also  found  that  just  as  in 
health,  the  body  uses  carbohydrates  in 
preference  to  fat  or  protein  to  meet  the  in- 
creased demand  for  energy  in  typhoid 
fever.  This  teaches  the  necessity  of  a  pre- 
dominance of  carbohydrates  in  the  diet  of 
a  typhoid  fever  patient. 

Causes  of  Protein  Destruction.  It  is 
not  alone  increased  temperature  but  also 
a  toxic  destruction  of  protein  which  in- 
creases the  metabolism  of  protein  in  fever. 

10  Coleman.     Journal     Am.     Med.     Association.     Vol. 
LXIII.     No.  4.     1914.     P.  932. 


150  ISAAC  OTT:  FEVER 

The  intracellular  ferments  also  act  upon 
the  increased  amount  of  amino-acids  and 
break  them  up  and  thus  produce  an  in- 
creased elimination  of  nitrogen. 

CARBO-HYDRATE    METABOLISM 

It  TTas  found  out  by  May  and  Weber 
that  the  breaking  up  of  protein  may  be 
reduced  by  giving  carbo-hydrates.  Hence 
it  is  probable  that  with  the  increased  de- 
struction of  protein  in  fever,  the  glycogen 
also  undergoes  consumption  at  the  same 
time.  All  the  glycogen  is  consumed  in  the 
first  few  days  of  fever,  and  thus  partially 
increases  heat  production. 

METABOLISM   OF  FATS 

The  fats  like  the  glycogen  are  also  at- 
tacked in  fever,  but  preferably  the  glyco- 
gen. Experiments  lead  to  the  idea  that 
the  gradual  wasting  of  the  fat  is  not  due 
to  any  direct  action  on  the  fats,  but  rather 
to  partial  hunger.     Staehelin  does  not  be- 


TITERMOTAXIS  AND  METABOLISM      151 

lieve  that  the  using  up  of  fat  is  entirely 
due  to  partial  starvation. 

WATER    METABOLISM 

In  fever,  conduction  and  perspiration- 
evaporation  are  lessened ;  the  functions  of 
dissipation  do  not  act  to  maintain  equili- 
brium at  the  same  level,  whether  produc- 
tion of  heat  is  normally  increased  or  de- 
creased. The  continuous  vaso-constric- 
tion  reduces  conduction  and  radiation  of 
heat  from  the  skin.  The  cause  of  fever, 
vaso-constriction,  proceeds  from  the  in- 
terior. The  perspiration  is  lessened,  and 
here  we  have  another  source  of  diminished 
radiation  of  heat.  The  water  from  the 
lungs  is  not  diminished  in  fever. 

Schwenkenbecker  and  Inagaki  ^^  show 
that  insensible  perspiration  in  fever  is  as 
great  as  in  health,  and  that  there  is  no  ac- 
cumulation of  water  in  the  body,  as  held 

11  Schwenkenbecker  u.  Inagaki.     Archie,  f.  Ea^p.  Path, 
u.  PJiarmakol.     1906.     B.  54,  p.  1G8. 


152  ISAAC  OTT:  FEVER 

by  Von  Leyden.  However,  the  urine  is 
decreased  in  quantity. 

Lang  ^2  has  shown  that  the  elimination 
of  sweat  is  diminished  during  the  eleva- 
tion of  temperature  in  man,  but  becomes 
normal  at  the  height  of  the  fever,  whilst 
in  some  cases  there  is  increased  evapora- 
tion from  the  lungs. 

In  Staehilin's  dog  infected  with  surra, 
the  total  intake  of  water  was  9030,  whilst 
the  total  outgo  was  11225,  making  an  in- 
crease of  21955,  or  calculated  by  metabol- 
ism, 1880.  There  was  certainly  no  reten- 
tion of  water  here. 

Von  Noorden  states  that  in  fever  the  or- 
ganism eliminates  by  the  lungs  more 
water,  even  during  fasting,  than  a  healthy 
individual  does  after  a  meal ;  the  augmen- 
tation amounts  to  about  50%'.  The  in- 
crease is,  however,  small. 

i2l^ng.     Archiv.    f.    Klin.    Med.    1903.     Band    79,    p. 
343. 


TIIERMOTAXIS  AND  METABOLISM     153 

PURIN    METABOLISM 

It  was  shown  by  Erben  that  xanthin 
bodies  and  animo-acids  are  increased  in 
fever  but  in  a  degree  varying  with  the 
character  of  the  disease. 

A.  R.  Mandel  ^^  found  in  so-called  aseptic 
or  surgical  fevers  that  there  is  a  large  in- 
crease of  the  purin  bases  in  the  urine  of 
patients  fed  with  milk.  The  temperature 
rises  and  falls  with  the  quantity  of  purin 
bases  eliminated.  Mandel  also  showed 
that  subcutaneous  injection  of  40  milli- 
grams of  xanthin  caused  a  marked  rise  in 
the  temperature  of  a  monkey,  and  that  a 
strong  decoction  of  60  grams  of  coffee 
caused  slight  fever  in  a  man  not  used  to 
it. 

Ott  and  Scott  ^^  found  guanin,  adenin 
and  hypo-xanthin  caused  an  elevation  of 

13  Mandel.     American    Journal    of    Physiology.     1904. 
Vol.  X,  p.  452. 

14  Ott  and  Scott.     Tlie  Medical  Bulletin.     Oct.,   1907. 


154  ISAAC  OTT:  FEVER 

temperature  in  rabbits,  whilst  uric  acid 
did  not. 

ACETONE  BODIES  AND  ACIDS  IN  FEVER 

Beta-oxybutyric  acid,  diacetic  acid  and 
acetone  have  been  found  in  the  urine  of 
patients  with  increased  temperature,  but 
of  the  three  bodies  acetone  is  more  fre- 
quently present. 

It  was  noted  by  Eegnard  and  Greffert 
and  also  by  Minkowski  and  Kraus  that  the 
amount  of  carbon  dioxide  in  venous  blood 
was  diminished.  It  was  supposed  to  be 
due  to  increased  formation  of  acid  in  the 
body.  Ammonia  was  also  increased,  and 
it  would  lead  us  to  think  that  there  was  an 
acid  poisoning. 

CHLORIDES   AND  PHOSPHATES   IN   FEVER 

Redtenbacher  first  noted  a  retention  of 
chlorides  in  the  body,  and  this  has  been 
confirmed  by  several  observers. 

In  pneumonia   it  was   found   that   the 


THEHMOTAXIS  AND  METABOLISM      155 

amount  of  sodium  chloride  in  the  urine 
was  very  greatly  diminished  before  the 
crisis.  After  the  crisis,  it  is  excreted  to 
a  considerable  extent.  Von  Limbeck, 
Schwarz,  Von  der  Berg  and  Moraczewski 
regard  the  chloride  excretion  as  inversely 
proportional  to  that  of  phosphoric  acid, 
that  retention  of  chlorine  takes  place  in 
consequence  of  increased  phosphoric  acid 
elimination,  the  retained  chloride  keep- 
ing up  an  isotonic  condition  in  the 
blood. 

Fever  consists  of  at  least  two  main 
characters — thermogenic  and  toxo  genie. 
As  to  the  temperature,  there  is  an  agent 
which  deranges  the  harmony  of  the  ther- 
mo-inhibitory,  thermogenic  and  thermo- 
lytic  apparatuses,  by  which  in  the  initial 
stage  the  metabolism  of  the  tissues  is 
usually  temporarily  increased  and  this  in- 
crement is  usually  greater  than  that  gen- 
ated  upon  a  restricted  amount  of  nutri- 
ment.    It   is    during   the   chill   that   heat 


156  ISAAC  OTT:  FEVER 

dissipation  is  temporarily  diminislied,  but 
afterwards  it  usually  follows  the  fluctua- 
tions of  heat  production.  The  tuber 
cinereum  and  the  corpus  striatum  play 
the  most  important  part  in  the  thermo- 
genic process  and  of  these  two  the  tuber 
is  more  important.  Neither  increased 
production  nor  diminished  dissipation  are 
necessary  to  constitute  fever,  as  is  shown 
where  heat  production  diminished  al- 
though the  temperature  is  elevated.  In 
another  experiment  of  mine  on  lower  ani- 
mals, at  one  period  the  temperature  was 
subnormal,  yet  the  heat  production  was 
greatly  increased  above  that  seen  on  a 
similar  period  of  the  preceding  day.  As 
to  the  other  symptoms  in  fever,  they  are 
caused  by  the  toxines,  chemical  substances 
affecting  every  cell. 

The  toxines  stimulate  the  cells  causing 
increased  metabolic  change  and  consump- 
tion of  energy.  Hence  the  true  theory  of 
fever  is  a  neurotoxogenic  process. 


THERMOTAXIS  AND  METABOLISM     157 

That  there  is  no  increased  production 
of  heat  in  the  stages  of  continued  fever, 
but  only  a  disarranged  regulation  of  heat 
is  quite  evident  to  anyone  who  has  stood 
by  the  bedside  of  a  typhoid  fever  case  in 
its  terminal  stages,  with  a  high  tempera- 
ture, when  the  body  looks  more  like  a 
cadaver  than  like  a  living  being  throbbing 
with  the  fullness  of  blood  and  life.  To 
imagine,  despite  the  paucity  of  food,  the 
wasting  of  the  cells  of  the  muscles  and 
of  the  viscera,  the  fever  is  due  to  in- 
creased production  of  heat  is  ridiculous. 

IS   FEVER    NOXIOUS    OR   BENEFICIAL? 

It  has  been  shown  by  Eolly  and  Melt- 
zer  ^^  and  Luedke  ^^  that  animals  heated 
up  to  40°,  after  receiving  daily  subcutane- 
ous injection  of  one-fourth  to  one-half  the 
fatal  dose  of  either  staphylococci,  pneumo- 

15  Roily  and  Meltzer.  Deutsch.  Archiv.  f.  Klin.  Med. 
1908.     XCIV.     335. 

i«  Luedke.  Deutsch.  Archiv.  f.  Klin.  Med.  1909. 
XCV.     425. 


158  ISAAC  OTT:  FEVER 

cocci  or  bacilli  coli  communis,  lived  longer, 
and  one-half  of  tliem  survived,  whilst  all 
the  control  animals  died. 


INDEX  OF  AUTHOES 


Andrews,  102 
Aronsohn,   19,   130,   142 
d'Arsonval,  16,  32 
Atwater,   17 
Auerbach,  82 
Avroroff,  P.  P.,  113 

Babak,  83 

Barbour,  H.  G.,  22,  23 
Bechterew,   27 
Benedict,  F.  G.,  17,  113 
Berg,  J.  F.,  106 
Boeke,  38 
Boldyreff,  68 
Botezat,   38 
Brodie,   16 


Cajal,  30 
Camus,  J.,  26 
Cannon,   76 
Carter,  W.  A.,  20,  89 
Chesnoeoff,   87 
Chvostek,    87 
Citron,   28 
Cloetta,  29 
Coleman,  148,  149 
Collmar,   32,   96 
Crawford,   15 
Crile,   73,    74,   75,   76, 
78,   79,  80 


Gushing,  69 

Dana,   35 
De  Boer,  38 
Despretz,   15 
Doeblin,  70,  71 
DuBois,  Eugene,  66,  67, 
Dulong,   15,   102 

Edinger,   31 
Eimden,  50 
Ekholm,  65 
Elias,  70 
Erben,  153 
Eulenburg,  22,  36,  90 

Favre,   102 

Fleischman,   70,   71 

Frank,  44 

Freund,  43,  46,  49,  50,  51 

Frumerie,  K.,  70,  71 

Fiirbringer,  147 


Galileo,  17 
Geffert,   154 
Gley,  74 
Graham,  148 
77,       Grafe,  E.,  43,  49 
Grehant,  87 
159 


160 


INDEX  OF  AUTHORS 


Hare,  92 
Hattwich,  87 
Helmholtz,   104 
Hirn,  G.  A.,  16 
Hirsch,  42,  43,   136,   138 

Inagaki,  151 
Isenschmid,   25,   28,  29 
Ito,  43 

Jacoby,    25 

Kocher,   148 

Kraus,  87,  154 

Krehl,   28,   97,    137,    141 


MacAlister,  Donald,  45,  95 
Mandel,  A.  R.,  153 
Maragliano,  87 
Marchand,   50 
Marey,  110 
Matthes,  97 
May,  145,  150 
Meltzer,   157 
Minkowski,  154 
Moraczewski,155 
Miiller,  136,  138 
Murri,  83 

Nebelthan,  52 
Nicolaides,  57 


Landois,  22,  36,  90 

Lang,    152 

Langlois,  87,   105 

La  Place,   15 

Latzow,  35 

Laulanie,  16 

Lavoisier,   15 

Leathes,    148 

Le  Fevre,  16 

Leschke,  28 

Leyden,  82,  87 

Liehaeheff,  A.  A.,  113,  117 

Liefman,  50 

Liebermeister,   82,   87,    110 

Liljestrand,  G.,  70,  71 

Limbeck,  von,  155 

Linsen,   148 

Loewi,  O.,  68,  87 

Luedke,    157 

Lukjanow,  45 

Lusk,  142,  143 

Liithje,  50 


Page,  36 
Pari,  47 

Pettenkofer,  17 
Pflueger,   144 
Porcelli-Titone,  84 
Poulton,  148 
Prizbram,   147 
Prince,  23 

Quinqaud,  87 

Redtenbacher,   154 
Regnar,  87 
Regnard,  154 
Regnault,  16 
Reichert,   92 
Reichet,  21 
Richet,  16 
Richter,    139 
Riethus,   87 
Robitsehek,  147 
Roemer,  25 


INDEX  OF  AUTHORS 


161 


Roily,    42,    43,    137,    138, 

141,  142,  157 
Rosenthal,  C,  87 
Rosenthal,  T.,  87 
Roussy,  26 
Riibner,  65 
Rumford,    102 

Sachs,   19 
Sakovic,  27 
Salkowsky,   147 
Sanctoriiis,   17 
Sawadowsky,  52 
Schlagintiweit,  46,  51 
Schmid,  148 
Schnitzler,  25,  29 
Schultz,  137 
Sclmltze,  42,  70 
Sclnvartz,   155 
Schwenkenbecker,    151 
Scott,   48,   69,   71,   72,   73, 

74,  140,  153 
Senator,  82,  83,  139 
Shaffer,  147,  148 
Sharpe,   147 
Silbermann,  102 
Silberstein,  51 
Simon,  147 
Sinelnikow,  41,  46 
Smith,  Robert  M.,  45 
Staehlin,   145,   150 


Stefani,  47 
Strassmann,  49 
Streerath,  26,  43 
Sternberg,  35 

Titone-Rorcelli,       84,       85, 

86,  88 
Traiibe,  82,  87,   110 
Tscheschichin,  82 
Tscheschokow,  47 
Tyndall,  14 

Vaughn,  97 
Van  Helmont,  14 
Virchow,  81 
Volt,  17,  32,  44 
Von  der  Berg,  155 
Von  Limbeck,  155 
Von  Noorden,    152 

Wachsmuth,  82 
Wahl,  87 
Waser,  29 
Weber,  150 
Wertheim,  87 
Weselko,  68 
White,  W.  Hale,  36 
Wing,   22 
Wood,  H.  C,  36,  92 

Zuelzer,  147 


GENEEAL  INDEX 


Acetone  bodies  and  acids 
in  fever,   154 

Addison's  disease,  74 

Adrenalin,  Crile's  state- 
ments of  effects,  75 

Adrenalin,  effects  of  injec- 
tions of,  71,  72 

Adrenalin  in  the  blood, 
causes  of  increase  of,  7G 

Adrenals,  effects  of  re- 
moval of,  50,  70-74 

Albumoses,  effects  of  upon 
heat  production,  96,  97 

Artificial  fever  experi- 
ments, 90-96 

i 

Basedow's  disease,   67 

Calorimetrical  studies,  15, 
16,  24 

Calorimetry,  indirect,  16, 
17 

Calorimetry  of  malarial 
fever,  97 

Carbon  dioxide,  elimina- 
tion affected  by  temper- 
ature of  body,  27 

Carbo-hydrate  metabolism, 
150 

Causes  of  fever,  76 


163 


Centers  of  animal  heat, 
14-17 

Cerebral  centers,  thermo- 
f^enic  effects  when  ab- 
sent, 35 

Cerebral  centers,  control- 
ling thermotaxis,    18 

Cerebral  thermogenic  cen- 
ters, 22-30 

Characteristics  of  fever, 
155 

Chemical  regulation,  44, 
47,  52,  53 

Chlorides  and  phosphates 
in  fever,  154 

Corpora  striata,  effect  on 
heat  dissipation  by  re- 
moval of,  59 

Corpus  striatum  and  ther- 
motaxis,  18,  20,  21,  22 

Corpus  striatum,  effects 
of  local  heating  or  cool- 
ing of,  23 

Cortical  thermogenic  cen- 
ters, 36-38 

Cruciate  nucleus,  18 

Curarization,  effects  of, 
43-44 

Evaporation  t  h  r  o  u  g  h 
sweat  glands,  65 


164 


GENEKAL  INDEX 


Exophthalmic  goiter,  67 
Experiments      determining 
thermogenic   center,    19 

Farad ic  current,  effects  of 
applying  to  tuber  cin- 
ereum,  59-00 

Easting,  effects  of  on  tem- 
perature, 70 

Fear  a  cause  of  fever,  76 

Fever  caused  by  fear,  76 

Fever,  destructive  of  bac- 
teria, 75 

Fever  in  man,  97 

Fever,  noxious  or  benefi- 
cial?   157 

Fever  observations,  126- 
136 

Fever-producing  agents, 
84-85 

Gaseous  exchange  in  fever, 

87,   125,  133 
Glycogen        investigations, 

136 
Graves'  disease,  79 

Heat,  early  theories  as  to 
source  of,  14-17 

Heat  dissipation  through 
the  skin,  65 

Heat  loss  by  radiation  and 
evaporation,    123 

Heat  of  animals,  Lavois- 
ier's discoveries,  15 

Heat  plienomena,  methods 
of  studying,  17 


Heat  production  and  heat 

dissipation,  88 
Heat    production    and    the 

spinal  cord,  32 
Heat    production,    effected 

by     partial     destruction 

of  spinal  cord,  33 
Heat  production,  effects  on 

of  vagal  section,  40-54 
Heat    production    in    nor- 
mal  conditions,  89 
Heat  regulating  fibers,   40 
Heat  regulation  and  sleep, 

66 
Hyperthermia,   81-88 

Infundibulin  injections,  ef- 
fects of  on  temperature, 
69 

Iodine,  effect  of,  74 

lodothvrin  doses,  effects 
of,  74 

Kinetic  system,  results  of 
excessive  activity  of,  80 

Liver,  as  source  of  heat 
production,  42 

Malarial  fever,  calorimetry 
of,   97 

Malarial  fever  investiga- 
tions.  117 

^Metabolism,  first  school 
for,  17 

Metabolism   in  fever,   136 

Metabolism   of  fats.   150 


GENERAL  INDEX 


165 


Mid-brain  thermogenic 

centers,  27-31 

Morphine,  Crile's  findings 
of  efl'ects  of,  75,  70 

Muscle,  tlierniogenic  func- 
tion in,  45 

Myenteric  plexus,  ollccts 
of  extirpation  of,  70,71 

Myxa^dema,  74 

Naphthylamine,    141 
Nerve    centers    controlling 

thermotaxis,  18 
Nerves   thermotaxic,   38-40 
Nissl  substance,  77-79 
Nitrogen  and  animal  heat, 

15 
Nitrogen,     urinary,     cause 

of  increase,  20 

Optic  thalami,  a  thermo- 
genic center,  23 

Oxygen  and  animal  heat, 
15,  IC 

Oxygen,     consumption     of, 

io 

Peptones,    effects    of    upon 

heat   production,   1)0,   5)7 
Pituitary,     efreots     of     on 

temperature  by  removal, 

01) 
PolypnaMc    center,    57-00 
Protein  destruction,  causes 

of,  140 
Protein  fever,  96 
Protein  metabolism,  142 


Purin   metabolism,    153 

Respiratory  studies,  15,  IG 
Kumford's      compensation, 
103 

Septic  fever,  98 

Shock,   pathology  of,   80 

Sleep,  efTect  of  on  boat 
regulation,    00 

Solar  plexus,  efi'ects  of  ex- 
tirpation of,  70,  71 

Spinal  cord  and  Co:;,  32 

Spinal  cord  and  heat  pro- 
duction,  32 

Spinal  cord,  efTect  on  heat 
production  by  partial 
destruction,    33 

Spinal  cord,  elVeet  on  tem- 
perature after  section, 
44 

Spinal  cord,  thermogenic 
centers  in,  32 

Splanchnics,  and  heat  pro- 
duction,   42 

Splanehnicotoniy,  eU'eets 
of,    70 

Strychnia  and  lieal  pro- 
duction, 43 

Sudorific   secretion,    64 

Sugar  in  blood,  relation  of 
to  temperature,  51 

Surface   radiation,    05 

Sweat  centers  and  glands, 
04 

Sylvian   nucleus,   IS 

Sympathetics,  effects  of  ex- 
cision  of,  48 


166 


GENERAL  INDEX 


Temperature,  definition  of, 
88 

Thermogenesis  and  con- 
traction, relations  of,  46 

Thermogenic  function  in 
muscle,  45 

Thermogenic  centers,  19-23 

Thermogenic  centers,  clas- 
sification of,  38 

Tliermogenic  centers,  dis- 
covery of,  19,  23 

Thermogenic  centers  in 
the  spinal  cord,   32-35 

Thermo-inhibitory  centers, 
36 

Thermolysis,  57-62 

Thermotaxic  fibers,  52-54 

Thermotaxic   nerves,   38-40 

Thermotaxis,  controlling 
nervous  centers,  19 

Thyroidectomized  animals, 
temperature  of,  68 

Thyroids.  efi"ects  on  heat 
regulation  by  removal 
of,  68 

Titone's  hypothesis  on  liy- 
perthermia  of  fever,  86 


Tuber  cinereum  and  ther- 
motaxis,  18,  23 

Tuber  cinereum,  eff"ect  of 
applying  faradic  cur- 
rent, 59-60 

Tuber  cinereum,  effect  on 
heat  dissipation  by  re- 
moval of,  59 

Tuber  cinereum,  functions 
of,  31 

Tuber  cinereum.  vaso-tonic 
action  of,  62 

Vagal    section,    effects    of, 

40-54 
Vaso-tonic  action  of  tuber 

cinereum,  62 
Visceral  glands,  as  sources 

of  heat,  41-43 

Water  metabolism,  151 

Water,  regulating  mechan- 
ism in  the  animal.  27 

Watery  vapor,    125 

Wood's  experiments  in  ar- 
tificial   fever,    90-96 


MEDICAL  MONOGRAPHS 

PUBLISHED  BY 
PAUL  B.  HOEBER 

67-69   EAST   59th   St.,   NEW   YORK 

This  catalogue  comprises  only  our  own  publications.  It 
will  be  noticed  that  particular  care  has  been  exercised  in  the 
selection  of  Monographs  of  timely  interest. 

We  are  always  glad  to  consider  the  publication  of  new  and 
original  medical  works.  Correspondence  with  Authors  is  in- 
vited. 

ADAM — Asthma  and  Its  Radical  Treatment.  By  James 
Adam,  M.A.,  M.D.,  F.R.C.P.S.  Hamilton.  Dispensary  Aural 
Surgeon,  Glasgow  Royal  Infirmary.  8vo,  Cloth,  viii+184 
pages,  Illustrated   $1.50  net. 

ARMSTRONG— I.  K.  Therapy,  With  Special  Reference  to 
Tuberculosis.  By  W.  E.  M.  Armstrong,  MA.,  M.D. 
Dublin.  Bacteriologist  to  the  Central  London  Ophthalmic 
Hospital,  Late  Assistant  in  the  Inoculation  Department,  St. 
Mary's  Hospital  Padding,  W. 
8vo,  Cloth,  x-f-93  pages,  Illustrated $1.50  net. 

BEDDOES — Syphilis,  Its  Diagnosis,  Prognosis,  Preven- 
tion and  Treatment.  By  Thomas  Hugh  Beddoes,  M.B., 
B.C.  Camb.,  F.R.C.S.  Eng.  Surgeon  to  the  London  Hos- 
pital for  Diseases  of  the  Skin.  Surgeon  to  the  Westminster 
General  Dispensary.  Registrar,  London  Lock  Hospital ;  Fel- 
low of  the  Royal  Society  of  Medicine;  Fellow  of  the  Trop- 
ical Society.     i2mo,  Cloth,  224  pages   $2.00  net. 

BIGG — Indigestion,  Constipation  and  Liver  Disorder.     By 

G.  Sherman  Bigg,  Fellow  of  the  Royal  College  of  Sur- 
geons ;  Fellow  of  the  Royal  Institute  of  Public  Health ;  Late 
Surgeon  Captain,  Army  Medical  Staff;  Surgeon  Allahabad 
India.     i2mo.   Cloth,   viii-f-168  pages    $1.50  net. 

BRUCE — Lectures  on  Tuberculosis  to  Nurses.     Based  on 
a  course  delivered  to  the   Queen  Victoria  Jubilee   Nurses. 
By  Olliver  Bruce,  M.R.C.S.,  L.R.C.P.,  Joint  Tuberculosis 
Officer,  County  of  Essex. 
i2mo,   Cloth,   134  pages.     Illustrated    $1.00  net. 

BRUNTON— Therapeutics    of    the    Circulation.     By    Sir 

Lauder  Brunton,  M.D.,  D.Sc,  LL.D.  Edin.,  LL.D.,  Aberd., 

F.R.C.P.,  F.R.S.     Consulting  physician  to  St.  Bartholomew's 

Hospital. 

Second   Edition,   entirely   revised.     Cloth,   xxiv-l-536   pages, 

1 10  illustrations    $2.50  net. 


HOEBEB'S  MEDICAL  MONOGRAPHS 

BULKLEY — Compendium  of  Diseases  of  the  Skin.  Based 
on  an  analysis  of  thirty  thousand  consecutive  cases.  With 
a  Therapeutic  Formulary,  by  L.  Duncan  Bulkley^  A.M., 
M.D.  Physician  to  the  New  York  Skin  and  Cancer  Hos- 
pital ;  Consulting  Physician  to  the  New  York  Hospital. 
8vo,  Cloth,  xviii+286  pages    $2.00  net. 

BULKLEY — Diet  and  Hygiene  in  Diseases  of  the  Skin. 
By  L.  Duncan  Bulkley,  A.M.,  M.D. 
8vo,  Cloth,  xvi-|-i94  pages    $2.00  net. 

CAUTLEY— The  Diseases  of  Infants  and  Children.     By 

Edmund   Cautley,   M.D.   Cantab.,   F.R.C.P.   Lond.     Senior 
Physician    to    the    Belgrave    Hospital    for    Children ;    Phy- 
sician to  the  MetropoHtan  Hospital;  etc. 
Large  8vo,  Cloth,  1042  pages $7.00  net. 

COOPER — Pathological  Inebriety.  Its  Causation  and 
Treatment.  By  J.  W.  Astley  Cooper.  Medical  Super- 
intendent and  Licensee  of  Ghyllwood  Sanatorium  near  Cock- 
ermouth,  Cumberland.  With  introduction  by  Sir  David 
Ferrier,  M.D.,  F.R.S. 
i2mo,  Cloth,  xvi+151  pages   $1.50  net. 

COOPER— The    Sexual    Disabilities    of    Man,    and    Their 
Treatment.     By  Arthur  Cooper.     Consulting  Surgeon  to 
the  Westminster  General  Dispensary;  Formerly  Surgeon  to 
the   Male  Lock  Hospital,   London. 
2nd  Edition,   i2mo.  Cloth,  viii-f-204  pages $2.00  net. 

CORBETT-SMITH— The    Problem    of    the    Nations.     A 

Study  in  the  Causes,  Symptoms  and  Effects  of  Sexual  Dis- 
ease, and  the  Education  of  the  Individual  therein.  By  A. 
Corbett-Smith,  Editor  of  "The  Journal  of  State  Medicine"; 
Lecturer  in  Public  Health  Law  at  the  Royal  Institute  of 
Public  Health.     Large  Svo,  Cloth,  xii+107  pages.  .$1.00  net. 

CORNET— Acute      General      Miliary      Tuberculosis.     By 
Professor  Dr.  G.  Cornet,  Berlin  and  Reichenhall.    Trans- 
lated by  F.  S.  Tinker,  B.A.,  M.B.,  etc. 
Svo,  Cloth,  viii  +  107  pages   $1.50  net. 

CROOKSHANK— Flatulence  and  Shock.     By  F.  G.  Crook- 
shank,  M.D.,  Lond.,   M.R.C.P.     Physician    (Out   Patients) 
Hampstead  General  and  N.  W.  Lond.  Hospital ;  Assistant 
Physician  The  Belgrave  Hospital  for  Children  S.W. 
Svo,  Cloth,  ivH-47  pages   $1.00  net. 

EDRIDGE-GREEN— The  Hunterian  Lectures  on  Colour- 
Vision  and  Colour  Blindness.  Delivered  before  the 
Royal  College  of  Surgeons  of  England  on  February  ist,  and 
3rd,  191 1.  By  Professor  F.  W.  Edridge-Green,  M.D.  Durh., 
F.R.C.S.  England.  Beit  Medical  Research  Fellow. 
Svo,  Cloth,  x-l-76  pages $1.50  net. 


HOEBER'S  MEDICAL  MONOGRAPHS 

EHRLICH — Experimental  Researches  on  Specific  Thera- 
peutics. By  Prof.  Paul  Ehrlich,  M.D.,  D.Sc.  Oxon. 
Director  of  the  Konigliches  Institut  fur  Experimentelle 
Therapie,  Frankfort.  The  Harben  Lectures  for  1907  of  The 
Royal  Institute  of  Public  Health. 
i6mo,   Cloth,   x-f95   pages    $1.00  net. 

EINHORN — Lectures    on    Dietetics.     By    Max    Einhorn, 
Professor    of    Medicine   at   the    New    York    Post-Graduate 
Medical  School  and  Hospital  and  Visiting  Physician  to  :he 
German  Hospital,  New  York. 
i2mo,  Cloth,  xvi-f-156  pages   $1.00  net. 

ELLIOT — Sclero-Corneal  Trephining  in  the  Operative 
Treatment  of  Glaucoma.  By  Robert  Henry  Elliot,  M.D., 
B.S.  Lond.,  Sc.D.  Edin.,  F.R.C.S.  Eng.,  Etc.  Lieut.  Colonel 
I. M.S.  Second  Edition.  8vo,  Cloth,  135  pages  33  illustra- 
tions     $3.00  }iet. 

EMERY— Immunity     and      Specific      Therapy.     By    Wm. 

D'EsTE  Emery,  M.D.,  B.Sc.  Lond.  Clinical  Pathologist  to 
King's  College  Hospital  and  Pathologist  to  the  Children's 
Hospital,  Paddington  Green ;  formerly  Assistant  Bacteriolo- 
gist to  the  Royal  Colleges  of  Physicians  and  Surgeons,  and 
sometime  Lecturer  on  Pathology  and  Bacteriology  in  the 
University  of  Birmingham. 
8vo,  Cloth,  448  pages,  with  2  ills $3-50  >Jct. 

adopted  by  the  lt.  s.  army 

GILES — Anatomy  and  Physiology  of  the  Female  Genera- 
tive Organs  and  of  Pregnancy.  By  Arthur  E.  Giles, 
M.D.,  B.Sc.  Lond.  M.R.C.P.  Lond;  F.R.C.S.  Ed.  Gynecologist 
to  the  Prince  of  Wales  General  Hospital,  Tottenham,  and 
Surgeon  to  the  Chelsea  Hospital  for  Women. 
Large  8vo,  24  pages  with  manikin $1.50  )tct. 

GREEFF — Guide  to  the  Microscopic  Examination  of  the 
Eye.  By  Professor  R.  Greeff.  Director  of  the  Uni- 
versity Ophthalmic  Clinique  in  the  Royal  Charity  Hospital. 
Berlin.  With  the  co-operation  of  Professor  Stock  and  Pro- 
fessor Wintersteiner.  Translated  from  the  third  German 
Edition  by  Hugh  Walker.  M.D.,  M.B..  CM.  Ophthalmic 
Surgeon  to  the  Victoria  Infirmary,  Glasgow. 
Large  8vo,  Cloth,  86  pages.  Illustrated   $2.00  net. 

HARRIS — Lectures  on  Medical  Electricity  to  Nurses.  An 
Illustrated  Manual  by  J.  Delpratt  Harris.  M.D.  Durh., 
M.R.C.S.  Senior  Surgeon  and  Honorary  Medical  OflFicer 
in  charge  of  the  Electrical  Department,  Royal  Devon  Hosp. 

i2mo.  Cloth,  88  pages.     Illustrated   $1.00  net. 

3 


HOEBER'S  MEDICAL  MONOGRAPHS 

HOFMANN-GARSON— Remedial  Gymnastics  for  Heart 
Affections.  Used  at  Bad-Nauheim.  Being  a  translation 
of  "Die  Gymnastik  der  Herzleidenden"  von  Dr.  Med. 
Julius  Hofmann  und  Dr.  Med.  Ludwig  Pohlman.  Berlin 
and  Bad-Nauheim.  By  John  George  Garson,  M.D.  Edin., 
etc.  Physician  to  the  Sanatoria  and  Bad-Nauheim,  Evers- 
ley,  Hants.  With  51  full-page  illustrations  and  diagrams. 
Large  8vo,  Cloth,  xvi-|-i28  pages  $2.00  net. 

HOWARD— The   Therapeutic   Value   of   the   Potato.     By 

Heaton   C.   Howard,  L.R.C.P.  Lond,,  M.R.C.S.  Eng.    8vo, 
paper,  vi+31   pages.  Illustrated    50c 

JELLETT— A    Short   Practice   of   Midwifery   for   Nurses. 

Embodying  the  treatment  adopted  in  the  Rotunda  Hospital, 
Dublin.  By  Henry  Jellett,  B.A.,  M.D,  (Dublin  Univer- 
sity) F.R.C.P.L,  Master  Rotunda  Hospital;  Extern  Exam- 
iner in  Midwifery  and  Gynecology,  Victoria  University, 
Manchester;  Late  King's  Professor  of  Midwifery;  Univer- 
sity of  Dublin.  With  six  plates  and  169  illustrations  in  the 
text,  also  an  appendix,  a  glossary  of  Medical  Terms,  and 
the  Regulations  of  the  Central  Midwives  Board. 
i2mo,  Cloth,  xvi-f-508  pages   $2.50  net. 

KENWOOD— Public  Health  Laboratory  Work.  By 
Henry  R.  Kenwood,  M.B.,  F.R.S.  Edin.,  P.P.H..  F.C.S., 
Chadwick.  Professor  of  Hygiene  and  Public  Health,  Uni- 
versity of  London ;  Medical  Officer  of  Health  and  Public 
Analyst  for  the  IMetropolitan  Borough  of  Stoke  Newington ; 
Examiner  in  Public  Health  to  the  Royal  College  of  Phy- 
sicians and  Surgeons,  London,  etc. 
6th  Edition,  8vo.,  Cloth,  418  pages.     Illustrated.  ..  .$4.00  net. 

LEWERS — A  Practical  Textbook  of  the  Diseases  of 
Women.  By  Arthur  H.  N.  Lewers,  M.D.  Lond.  Senior 
Obstetric  Physician  to  the  London  Hospital ;  Late  Exam- 
iner in  Obstetric  Medicine  at  the  LIniversity  of  London ; 
University  Scholar  &  Gold  Medallist  in  Obstetric  Medicine. 
London  University,  etc.  With  258  illustrations,  13  colored 
plates,  5  plates  in  black  and  white. 
7th  Edition,  8vo,  Cloth,  xii+540  pp $4-oo  net. 

LEWIS— Clinical  Disorders  of  the  Heart  Beat.  A  Hand- 
book for  practitioners  and  Students.  By  Thomas  Lewis, 
M.D.,  D.Sc,  F.R.C.P.  Assistant  Physician  and  Lecturer  in 
Cardiac  Pathology,  University  College  Hospital.  Physician 
to  Out-Patients,  City  of  London  Hospital  for  Diseases  of 
the  Chest.  SECOND  EDITION. 
8vo,  Cloth,   116  pages.     Illustrated   $2.00  net. 


HOEBER'S  MEDICAL  MOXOGRAPHS 

LEWIS — Lectures  on  the  Heart.  Comprising  the  Herter 
Lectures  (Baltimore),  a  Harvey  Lecture  (New  York)  and 
an  address  to  the  Facuky  of  Medicine  at  McGill  Univer- 
sity (Montreal),  by  Thomas  Lewis,  M.D.,  F.R.C.P.  Phy- 
sician, City  of  London  Hospital;  Assistant  Physician  and 
Lecturer  in  Cardiac  Pathology,  University  College  Hos- 
pital, London.     With  83  illustrations $2.00  net. 

LEWIS— The  Mechanism  of  the  Heart  Beat.  With  spe- 
cial reference  to  its  Clinical  Patholog>-.  By  Thomas  Lewis, 
M.D.,  D.Sc,  M.R.C.P.  Lecturer  in  Cardiac  Pathology,  Uni- 
versity College  Hospital  Medical  School ;  Physician  to  Out- 
Patients.  City  of  London  Hospital  for  the  Diseases  of  the 
Chest.     Large  8vo,  Cloth,  295  pages,  227  Illus.  . .  .$7.00  net. 

McCLURE — A    Handbook    of    Fevers.     By    J.    Campbell 
McClure.  M.D.,  Glasgow.     Physician  to  Out-Patients,  The 
French  Hospital,  and  Physician  to  the  ^Margaret  Street  Hos- 
pital for  Consumption  and  Diseases  of  the  Chest,  London. 
8vo,  Cloth,  470  pages,  with  charts   $3.50  net. 

McCRUDDEN— The   Chemistry,   Physiology  and   Pathol- 
ogy   of    Uric    Acid,    and   the    Physiologically    Important 
Purin  Bodies.     With  a  discussion  of  the  ^Metabolism  in 
Gout.     By  Francis  H.  McCrudden, 
ijmo.  Paper.     318  pages   $2.00  net. 

McKISACK — Systematic-Case  Taking.     A  Practical  guide 
to    the    examination    and    recording    of   medical    cases.     By 
Henry  Lawrence  McKisack,  M.D.,  M.R.C.P.  Lond.     Phy- 
sician to  the  Royal  A^ictoria  Hospital,  Belfast. 
i2mo.  Cloth,  166  pages  $1.50  net. 

MACKENZIE — Symptoms   and   their    Interpretation.     By 

James  Mackenzie,  M.D.,  LL.D.,  Aber.  and  Edin.     Lecturer 

on  Cardiac  Research,  London  Hospital. 

Svo,  Cloth.     Illustrated,     xxii+304  pages  $3.00  )iet. 

MACMICHAEL— The  Gold  Headed  Cane.  By  William 
Macmichael.  Reprinted  from  the  2nd  Edition,  with  a 
Preface  by  Sir  William  Osler  and  an  Introduction  by  Dr. 
Francis  R.  Packard. 

Printed  in  large  Scotch  type  on  a  special  heavy  weight 
paper,  5^  by  7^  inches,  bound  in  blue  Italian  handmade 
paper,  with  ivory  linen  back  and  corners,  gilt  top,  square 
back,  and  gold  stamping  on  back  and  side $3.00  )iet. 

MARTINDALE     and     WESTCOTT— "Salvarsan"     "606" 
(Dioxy-Diamino    Arsenobenzol)     Its    Chemistry,    Phar- 
macy and  Therapeutics.     By  W.   Harrison   Martindale, 
Ph.D.  Marburg  F.C.S.,  and  W.  Wynn  Westcott,  M.B. 
Svo,  Cloth,  xvi+76  pages   $1.50  net. 

5 


HOEBER'S  MEDICAL  MONOGRAPHS 

MINETT — Diagnosis    of    Bacteria    and    Blood    Parasites. 

By  E.  P.  MiNETT,  M.D.,  D.P.H.,  D.T.M.  and  H.,  M.R.C.S., 
L.R.C.P.     Assistant  Government  Medical  Officer  of  Health 
and  Bacteriologist  British  Guiana. 
i2mo,    Cloth    viii+8o    pages    $i.oo  «^^. 

MURRELL— What    to    do    in    Cases    of    Poisoning.     By 

William  Murrell,  M.D.,  F.R.C.P.  Senior  Physician  to 
the  Westminster  Hospital ;  Lecturer  on  Clinical  Medicine 
and  joint  lecturer  on  the  principles  and  practice  of  medi- 
cine ;  Late  examiner  in  the  Universities  of  Edinburgh,  Glas- 
gow and  Aberdeen,  and  to  the  Royal  College  of  Physicians. 
Eleventh  Edition,  i6mo,  Cloth,  283  pages $1.00  net. 

OLIVER — Lead  Poisoning:  From  the  Industrial,  Med- 
ical and  Social  Point  of  View.  Lectures  delivered  at  the 
Royal  Institute  of  Public  Health.  By  Sir  Thomas  Oliver, 
M.A.,  M.D.,  F.R.C.P.  Consulting  Physician,  Royal  Victoria 
Infirmary,  and  Professor  of  the  Principles  and  Practice  of 
Medicine,  University  of  Durham  College  of  Medicine,  New- 
castle-upon-Tyne, Late  Medical  Expert,  Dangerous  Trades 
Committee ;  Home  Office. 
Large  i2mo.  Cloth,  294  pages $2.00  net. 

OSLER— Two  Essays.  By  Sir  William  Osler,  M.D. 
Regius  Professor  of  Medicine  at  Oxford. 

Vol.  I.     A  Way  of  Life.     An  Address  to  Yale  Students, 
Sunday     Evening,     April     20th,     1913.     i6mo,     Cloth,     61 

pages 50C  net. 

Vol.  2.     Man's  Redemption  of  Man.     A  Lay  Sermon, 
McEwan   Hall,   Edinburgh,    Sunday,   July  2d,    1910.     i6mo, 

Cloth,  63  pages    50c  net. 

The  set  neatly  bound  and  boxed $1.00  net. 

(A  handsome  presentation  set.) 

OTT — Fever,  Its  Thermotaxis  and  Metabolism.  By  Isaac 
Ott,  A.m.,  M.B.  Professor  of  Physiology  in  the  Medico- 
Chirurgical  College  of  Philadelphia ;  Ex-Fellow  in  Biology 
Johns  Hopkins  University;  Consulting  Neurologist,  Norris- 
town  Asylum,  Penna. ;  Ex-President  of  American  Neuro- 
logical Association,  Etc.,  168  pp.,  illus $1.50  net. 

PAGET — For  and  Against  Experiments  on  Animals.  Evi- 
dence before  the  Royal  Commission  of  Vivisection.  By 
Stephen  Paget,  F.R.C.S.  Hon.  Secretary  Research  De- 
fence Society.  With  an  introduction  by  The  Right  Hon. 
THE   EARL  OF  CROMER,   O.M.,   G.C.M.G.,   G.C.B. 

8vo,  Cloth,  Illustrated,    xii+344  pages   $1.50  f^^t- 

6 


HOEBER'S  MEDICAL  MONOGRAPHS 

PEGLER — Map  Scheme  of  the  Sensory  Distribution  of  the 
Fifth  Nerve  (Trigeminus)  with  Its  Ganglia  and  Connec- 
tions. By  L.  Hemingtox  Pf.cler,  M.D..  M.R.C.S.  Senior 
Surgeon,  Metropolitan  Ear,  Nose  and  Throat  Hospital,  Etc. 
Folded  in  Cloth  Binder,  4  ft.  i  in.  x  4  ft.  8  in...  .$8.00  net. 
Mounted  on   Rollers    $7.00  net. 

RAWLING — Landmarks  and  Surface  Markings  of  the  Hu- 
man Body.  By  L.  Bathe  Rawling,  M.B.,  B.C.  (Cant.) 
F.R.C.S.  (Lond.)  Surgeon  with  charge  of  Out-Patients, 
Late  Senior  Demonstrator  of  Anatomy  at  St.  Bartholomew's 
Hospital ;  Late  Assistant-Surgeon  to  the  German  Hospital, 
Dalston  ;  Late  Huntcrian  Professor  Royal  College  of  Sur- 
geons. England.  Etc.  FH-TH  EDITION. 
8vo,  Cloth,  31   plates,     xii+96  pages  of  text $2.00  net. 

RITCHIE— Auricular  Flutter.  By  William  Thomas 
RnrifFE.  .M.n.,  F.R.C.P.E.,  F.R.S.E.  Physician  to_  the 
Royal  Infirmary;  Lecturer  on  the  Practice  of  Medicine, 
School  of  Medicine  of  the  Royal  Colleges ;  Lecturer  on 
Clinical  Medicine  in  the  University  of  Edinburgh.  Large 
8vo,  Cloth,  xii-|-T44  pages,  21  plates,  107  Illus $3.50  net. 

RUTHERFORD— The  Ileo-Caecal  Valve.  By  A.  H. 
Rutherford,  M.D.     Edin. 

8vo,  Cloth,  63  pages  of  text,  23  full  page  plates  3  of  which 
are   colored    $2.25  net. 

SAALFELD — Lectures  on  Cosmetic  Treatment.  A  Man- 
ual for  Practitioners.  By  Dr.  Edmund  Saalfeld  of  Berlin. 
Translated  by  J.  F.  Dally,  M.A..  M.D.,  B.C.  Cantab.. 
M.R.C.P.  Lond.  Physician  to  the  St.  Marylebone  General 
Dispensary.  With  an  introduction  and  notes  by  P.  S. 
Abraham,  M.A.,  M.D.,  B.Sc,  F.R.C.S. I.,  Surgeon  for,  and 
Lecturer  on.  Diseases  of  the  Skin.  West  London  Hospital 
and  College.  Late  Surgeon  to  the  Skin  Hospital  Blackfriars. 
T2mo,  Cloth,  xii  +  186  pages.  Illustrated   $1.75  net. 

SCOTT— The  Road  to  a  Healthy  Old  Age.  Essays  by 
THO^rA.s  Bodley  Scott,  M.D.     i2mo.  Cloth.  104  pp. .$1.00  net. 

SENATOR  and  KAMINER— Marriage  and  Disease.  Be- 
ing an  Abridged  Edition  of  "Health  and  Disease  in  Rela- 
tion to  Marriage  and  the  Married  State."  By  Professor 
H.  Senator  and  Dr.  S.  Kaminer,  Translated  from  the 
German  by  J.  Dulp.erg,  'M.  D. 
8vo,  Cloth,  452  pages    $2.50  tiff. 

SMITH — Some  Common  Remedies,  and  Their  Use  in 
Practice.  By  Eustace  Smith.  M.D.  Fellow  of  the  Royal 
College  of  Physicians:  Senior  Physician  to  the  East  Lon- 
don Hospital  for  Children;  Consulting  Physician  to  the 
Victoria  Park  Hospital   for  Diseases  of  the  Chest. 

Svo,  Cloth,  viii+n2  pages   $1.25  net. 

7 


HOEBER'S  MEDICAL  MONOGRAPHS 

SQUIER  and  BUGBEE— Manual  of  Cystoscopy.     By  J. 
Bently    Squier,    M.D.     Professor   of   Genito-Urinary   Sur- 
gery,  New  York   Post-Gradtiate  Medical  School  and  Hos- 
pital, and  Henry  G.  Bugbee,  M.D. 
8vo,  Flex.  Leather,  xiv+ii7  PPv  26  colored  plates. $3.00  net. 

ADOPTED    BY    THE    U.    S.    ARMY 

STARK— The  Growth  and  Development  of  the  Baby.     A 

tabular  chart,  giving  the  result  of  personal  observation, 
verified  by  authoritative  data,  as  to  development,  weight, 
height,  etc.,  during  the  first  seven  years.  By  Morris 
Stark,  M.A.,  B.S.,  M.D.  Instructor  of  Pediatrics,  New 
York  Post  Graduate  Medical  School,  etc. 
Heavy  paper,  20  by  25  inches   50c  net. 

STEPHENSON— Eye-Strain   in   Every-day  Practice.     By 

Sidney     Stephenson,     M.B.,     CM.     Edin.,     D.O.     Oxon, 
F.R.C.S.   Edin.     Ophthalmic   Surgeon  to  the  Queen's   Hos- 
pital for  Children;  Editor  of  the  Ophthalmoscope. 
8vo,   Cloth,   x-f  139  pages    $1.50  "^^• 

STEPHENSON — A  Review  of  Hormone  Therapy.     1913. 

8vo,  Cloth,  viii+170  pages   $1.00  net. 

Bound    and    interleaved    edition    of   the    famous    "Hormone 
Number"  of  the  "Prescriber"    (Edinburgh). 

SWIETOCHOWSKI— Mechano-Therapeutics   in    General 
Practice.     By  G.  de  Swietochowski,  M.D'.,  M.R.C.S.  _  Fel- 
low of  the  Royal  Society  of  Medicine;   Clinical  Assistant, 
Electrical  and  Massage  Department  King's  College  Hosp. 
i2mo,  Cloth,  xiv+141   pp.,  31   Illustrations %i.so  net. 

TURNER  and  PORTER— The  Skiagraphy  of  the  Acces- 
sory Nasal  Sinuses.  By  A.  Logan  Turner,  M.D., 
F.R.C.S.E.,  F.R.S.E.  Surgeon  to  the  Ear  and  Throat  De- 
partment, The  Royal  Infirmary,  Edinburgh,  and  W.  G. 
Porter,  M.B.,  B.Sc,  F.R.C.S.E.  Surgeon  to  the  Eye  and 
Throat  Infirmary,  Edinburgh. 
Quarto,  Cloth,  45  pages  of  text.     39  plates $4.50  net. 

WANKLYN— How  to  Diagnose  Smallpox.  A  Guide  for 
General  Practitioners,  Post-Graduate  Students  and  Others. 
By  W.  McC.  Wanklyn,  B.A..  Cantab.,  M.R.C.S.,  L.R.C.P., 
D.P.H.  Assistant  Medical  Officer  of  the  London  County 
Council  and  formerly  Medical  Superintendent  of  the  River 
Ambulance  Service  (Small-pox). 
Svo,   Cloth,    102  pages.     Illustrated    $1.50  ;;r/. 

WHITE— The      Pathology     of     Growth.     Tumours.     By 

Charles  Powell  White,  M.C.  F.R.C.S.     Director,  Pilking- 
ton   Cancer   Research    Fund,    Pathologist  Christie   Hospital, 
Special  Lecturer  in  Pathology,  University  of  Manchester. 
Svo,  Cloth,  xvi  +  235  pages.     Illustrated    $3.5071^/. 


HOEBEB'S  MEDICAL  MONOGBAPHS 

WATSON — Gonorrhoea  and  its  Complications  in  the 
Male  and  Female.  By  David  Watson,  M.B.,  CM.,  Sur- 
geon Glasgow  Lock  Hospital,  Dispensary  Surgeon  for  Ve- 
nereal Diseases  Glasgow  Royal  Infirmary,  etc.,  etc. 
Cloth,  8vo.,  375  pages,  72  illustrations,  12  plates,  some  col- 
ored   $3.75  net. 

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'IMiis  book  is  due  on  the  date  indicated  below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing, 
as  provided  by  the  rules  of  the  Library  or  by  special  ar- 
rangement with  the  Librarian  in  charge. 


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